Author: "Kaprio, J. (Jaakko)" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Kaprio, J. (Jaakko)"' showing total 69 results

Start Over Author "Kaprio, J. (Jaakko)"

69 results on '"Kaprio, J. (Jaakko)"'

1. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study

Author: Lapatto, H. A. (Helena A. K.), Kuusela, M. (Minna), Heikkinen, A. (Aino), Muniandy, M. (Maheswary), van der Kolk, B. W. (Birgitta W.), Gopalakrishnan, S. (Swetha), Pöllänen, N. (Noora), Sandvik, M. (Martin), Schmidt, M. S. (Mark S.), Heinonen, S. (Sini), Saari, S. (Sina), Kuula, J. (Juho), Hakkarainen, A. (Antti), Tampio, J. (Janne), Saarinen, T. (Tuure), Taskinen, M.-R. (Marja-Riitta), Lundbom, N. (Nina), Groop, P.-H. (Per-Henrik), Tiirola, M. (Marja), Katajisto, P. (Pekka), Lehtonen, M. (Marko), Brenner, C. (Charles), Kaprio, J. (Jaakko), Pekkala, S. (Satu), Ollikainen, M. (Miina), Pietiläinen, K. H. (Kirsi H.), Pirinen, E. (Eija), Lapatto, H. A. (Helena A. K.), Kuusela, M. (Minna), Heikkinen, A. (Aino), Muniandy, M. (Maheswary), van der Kolk, B. W. (Birgitta W.), Gopalakrishnan, S. (Swetha), Pöllänen, N. (Noora), Sandvik, M. (Martin), Schmidt, M. S. (Mark S.), Heinonen, S. (Sini), Saari, S. (Sina), Kuula, J. (Juho), Hakkarainen, A. (Antti), Tampio, J. (Janne), Saarinen, T. (Tuure), Taskinen, M.-R. (Marja-Riitta), Lundbom, N. (Nina), Groop, P.-H. (Per-Henrik), Tiirola, M. (Marja), Katajisto, P. (Pekka), Lehtonen, M. (Marko), Brenner, C. (Charles), Kaprio, J. (Jaakko), Pekkala, S. (Satu), Ollikainen, M. (Miina), Pietiläinen, K. H. (Kirsi H.), and Pirinen, E. (Eija)
Abstract: Nicotinamide adenine dinucleotide (NAD⁺) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD⁺ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD⁺ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.
Published: 2023

2. Physical activity and health:findings from Finnish monozygotic twin pairs discordant for physical activity

Author: Kujala, U. M. (Urho M.), Leskinen, T. (Tuija), Rottensteiner, M. (Mirva), Aaltonen, S. (Sari), Ala-Korpela, M. (Mika), Waller, K. (Katja), Kaprio, J. (Jaakko), Kujala, U. M. (Urho M.), Leskinen, T. (Tuija), Rottensteiner, M. (Mirva), Aaltonen, S. (Sari), Ala-Korpela, M. (Mika), Waller, K. (Katja), and Kaprio, J. (Jaakko)
Abstract: Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.
Published: 2022

3. Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms

Author: Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)
Abstract: Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84–2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%–8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| < 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42–0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
Published: 2022

4. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Author: Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. (Stephen T.), Mitche, B. D. (Braxton D.), Nickerson, D. A. (Deborah A.), North, K. E. (Kari E.), Palotie, A. (Aarno), Park, C. J. (Cheol Joo), Psat, B. M. (Bruce M. Y.), Rao, D. C. (D. C.), Redline, S. (Susan), Reiner, A. P. (Alexander P.), Seo, D. (Daekwan), Seo, J.-S. (Jeong-Sun), Smith, A. V. (Albert, V), Tracy, R. P. (Russell P.), Kathiresan, S. (Sekar), Cupples, L. A. (L. Adrienne), Rotten, J. I. (Jerome, I), Morrison, A. C. (Alanna C.), Rich, S. S. (Stephen S.), Ripatti, S. (Samuli), Wilier, C. (Cristen), Peloso, G. M. (Gina M.), Vasan, R. S. (Ramachandran S.), Abe, N. (Namiko), Albert, C. (Christine), Almasy, L. (Laura), Alonso, A. (Alvaro), Ament, S. (Seth), Anderson, P. (Peter), Applebaum-Bowden, D. (Deborah), Arking, D. (Dan), Ashley-Koch, A. (Allison), Auer, P. (Paul), Avramopoulos, D. (Dimitrios), Barnard, J. (John), Barnes, K. (Kathleen), Barr, R. G. (R. Graham), Barron-Casella, E. (Emily), Beaty, T. (Terri), Becker, D. (Diane), Beer, R. (Rebecca), Begum, F. (Ferdouse), Beitelshees, A. (Amber), Benjamin, E. (Emelia), Bezerra, M. (Marcos), Bielak, L. (Larry), Blackwel, T. (Thomas), Bowler, R. (Russell), Broecke, U. (Ulrich), Bunting, K. (Karen), Burchard, E. (Esteban), Buth, E. (Erin), Cardwel, J. (Jonathan), Carty, C. (Cara), Casaburi, R. (Richard), Casella, J. (James), Chaffin, M. (Mark), Chang, C. (Christy), Chasman, D. (Daniel), Chavan, S. (Sameer), Chen, B.-J. (Bo-Juen), Chen, W.-M. (Wei-Min), Chol, M. (Michael), Choi, S. H. (Seung Hoan), Chuang, L.-M. (Lee-Ming), Chung, M. (Mina), Conomos, M. P. (Matthew P.), Cornell, E. (Elaine), Crapo, J. (James), Curtis, J. (Jeffrey), Custer, B. (Brian), Damcott, C. (Coleen), Darbar, D. (Dawood), Das, S. (Sayantan), David, S. (Sean), Davis, C. (Colleen), Daya, M. (Michelle), de Andrade, M. (Mariza), DeBaunuo, M. (Michael), Duan, Q. (Qing), Devine, R. D. (Ranjan Deka Dawn DeMeo Scott), Duggirala, Q. R. (Qing Ravi), Durda, J. P. (Jon Peter), Dutcher, S. (Susan), Eaton, C. (Charles), Ekunwe, L. (Lynette), Farber, C. (Charles), Farnaml, L. (Leanna), Fingerlin, T. (Tasha), Flickinger, M. (Matthew), Franceschini, N. (Nora), Fu, M. (Mao), Fullerton, S. M. (Stephanie M.), Fulton, L. (Lucinda), Gan, W. (Weiniu), Gao, Y. (Yan), Gass, M. (Margery), Ge, B. (Bruce), Geng, X. P. (Xiaoqi Priscilla), Gignoux, C. (Chris), Gladwin, M. (Mark), Glahn, D. (David), Gogarten, S. (Stephanie), Gong, D.-W. (Da-Wei), Goring, H. (Harald), Gu, C. C. (C. Charles), Guan, Y. (Yue), Guo, X. (Xiuqing), Haessler, J. (Jeff), Hall, M. (Michael), Harris, D. (Daniel), Hawle, N. Y. (Nicola Y.), Heavner, B. (Ben), Heckbert, S. (Susan), Hernandez, R. (Ryan), Herrington, D. (David), Hersh, C. (Craig), Hidalgo, B. (Bertha), Hixson, J. (James), Hokanson, J. (John), Hong, E. (Elliott), Hoth, K. (Karin), Hsiung, C. A. (Chao Agnes), Huston, H. (Haley), Hwu, C. M. (Chii Min), Jackson, R. (Rebecca), Jain, D. (Deepti), Jaquish, C. (Cashell), Jhun, M. A. (Min A.), Johnsen, J. (Jill), Johnson, A. (Andrew), Johnson, C. (Craig), Johnston, R. (Rich), Jones, K. (Kimberly), Kang, H. M. (Hyun Min), Kaufman, L. (Laura), Kell, S. Y. (Shannon Y.), Kessler, M. (Michael), Kinney, G. (Greg), Konkle, B. (Barbara), Kramer, H. (Holly), Krauter, S. (Stephanie), Lange, C. (Christoph), Lange, E. (Ethan), Laurie, C. (Cecelia), LeBoff, M. (Meryl), Lee, S. S. (Seunggeun Shawn), Lee, W.-J. (Wen-Jane), LeFaive, J. (Jonathon), Levine, D. (David), Levy, D. (Dan), Lewis, J. (Joshua), Li, Y. (Yun), Lin, H. (Honghuang), Lin, K. H. (Keng Han), Lin, X. (Xihong), Liu, S. (Simin), Liu, Y. (Yongmei), Lunetta, K. (Kathryn), Luo, J. (James), Mahaney, M. (Michael), Make, B. (Barry), Manichaikul, A. (Ani), Mansonl, J. (JoAnn), Margolin, L. (Lauren), Mathai, S. (Susan), McArdle, P. (Patrick), Mcdonald, M.-L. (Merry-Lynn), McFarland, S. (Sean), McHugh, C. (Caitlin), Mei, H. (Hao), Meyers, D. A. (Deborah A.), Mikulla, J. (Julie), Min, N. (Nancy), Minear, M. (Mollie), Minster, R. L. (Ryan L.), Musani, S. (Solomon), Mwasongwe, S. (Stanford), Mychaleckyj, J. C. (Josyf C.), Nadkarni, G. (Girish), Naik, R. (Rakhi), Naseri, T. (Take), Nekhai, S. (Sergei), Nelson, S. C. (Sarah C.), Nickerson, D. (Deborah), Connell, J. O. (Jeff O.), Connor, T. O. (Tim O.), Ochs-Balcom, H. (Heather), Pankow, J. (James), Papanicolaou, G. (George), Parkerl, M. (Margaret), Parsa, A. (Afshin), Penchey, S. (Sara), Perez, M. (Marco), Peters, U. (Ulrike), Phillips, L. S. (Lawrence S.), Phillips, S. (Sam), Pollin, T. (Toni), Post, W. (Wendy), Becker, J. P. (Julia Powers), Boorgula, M. P. (Meher Preethi), Preuss, M. (Michael), Prokopenko, D. (Dmitry), Qasba, P. (Pankaj), Qiao, D. (Dandi), Rafaels, N. (Nicholas), Raffield, L. (Laura), Rasmussen-Torvik, L. (Laura), Ratan, A. (Aakrosh), Reed, R. (Robert), Reganl, E. (Elizabeth), Reupena, M. S. (Muagututi Sefuiva), Rice, K. (Ken), Roden, D. (Dan), Roselli, C. (Carolina), Ruczinski, I. (Ingo), Russel, P. (Pamela), Ruuska, S. (Sarah), Ryan, K. (Kathleen), Sabino, E. C. (Ester Cerdeira), Sakornsakolpatl, P. (Phuwanat), Salzberg, S. (Steven), Sandow, K. (Kevin), Sankaran, V. G. (Vijay G.), Scheller, C. (Christopher), Schmidt, E. (Ellen), Schwander, K. (Karen), Schwartz, D. (David), Sciurba, F. (Frank), Seidman, C. (Christine), Seidman, J. (Jonathan), Sheehan, V. (Vivien), Shetty, A. (Amol), Shetty, A. (Aniket), Sheu, W. H. (Wayne Hui-Heng), Shoemaker, M. B. (M. Benjamin), Silver, B. (Brian), Silvermanl, E. (Edwin), Smith, J. (Jennifer), Smith, J. (Josh), Smith, N. (Nicholas), Smith, T. (Tanja), Smoller, S. (Sylvia), Snively, B. (Beverly), Soferlm, T. (Tamar), Streeten, E. (Elizabeth), Su, J. L. (Jessica Lasky), Sung, Y. J. (Yun Ju), Sylvia, J. (Jody), Sztalryd, C. (Carole), Taliun, D. (Daniel), Tang, H. (Hua), Taub, M. (Margaret), Taylor, K. D. (Kent D.), Taylor, S. (Simeon), Telen, M. (Marilyn), Thornton, T. A. (Timothy A.), Tinker, L. (Lesley), Tirschwel, D. (David), Tiwari, H. (Hemant), Vaidya, D. (Dhananjay), VandeHaar, P. (Peter), Vrieze, S. (Scott), Walker, T. (Tarik), Wallace, R. (Robert), Waits, A. (Avram), Wan, E. (Emily), Wang, H. (Heming), Watson, K. (Karol), Weir, B. (Bruce), Weiss, S. (Scott), Weng, L.-C. (Lu-Chen), Williams, K. (Kayleen), Williams, L. K. (L. Keoki), Wilson, C. (Carla), Wong, Q. (Quenna), Xu, H. (Huichun), Yang, I. (Ivana), Yang, R. (Rongze), Zaghlou, N. (Norann), Zekavat, M. (Maryam), Zhang, Y. (Yingze), Zhao, S. X. (Snow Xueyan), Zhao, W. (Wei), Zni, D. (Degui), Zhou, X. (Xiang), Zhu, X. (Xiaofeng), Zody, M. (Michael), Zoellner, S. (Sebastian), Daly, M. (Mark), Jacob, H. (Howard), Matakidou, A. (Athena), Runz, H. (Heiko), John, S. (Sally), Plenge, R. (Robert), McCarthy, M. (Mark), Hunkapiller, J. (Julie), Ehm, M. (Meg), Waterworth, D. (Dawn), Fox, C. (Caroline), Malarstig, A. (Anders), Klinger, K. (Kathy), Call, K. (Kathy), Mkel, T. (Tomi), Kaprio, J. (Jaakko), Virolainen, P. (Petri), Pulkki, K. (Kari), Kilpi, T. (Terhi), Perola, M. (Markus), Partanen, J. (Jukka), Pitkranta, A. (Anne), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Savinainen, K. (Kimmo), Kosma, V.-M. (Veli-Matti), Kujala, U. (Urho), Tuovila, O. (Outi), Hendolin, M. (Minna), Pakkanen, R. (Raimo), Waring, J. (Jeff), Riley-Gillis, B. (Bridget), Liu, J. (Jimmy), Biswas, S. (Shameek), Diogo, D. (Dorothee), Marshall, C. (Catherine), Hu, X. (Xinli), Gossel, M. (Matthias), Schleutker, J. (Johanna), Arvas, M. (Mikko), Hinttala, R. (Reetta), Kettunen, J. (Johannes), Laaksonen, R. (Reijo), Mannermaa, A. (Arto), Paloneva, J. (Juha), Soininen, H. (Hilkka), Julkunen, V. (Valtteri), Remes, A. (Anne), Klviinen, R. (Reetta), Hiltunen, M. (Mikko), Peltola, J. (Jukka), Tienari, P. (Pentti), Rinne, J. (Juha), Ziemann, A. (Adam), Waring, J. (Jeffrey), Esmaeeli, S. (Sahar), Smaoui, N. (Nizar), Lehtonen, A. (Anne), Eaton, S. (Susan), Landenper, S. (Sanni), Michon, J. (John), Kerchner, G. (Geoff), Bowers, N. (Natalie), Teng, E. (Edmond), Eicher, J. (John), Mehta, V. (Vinay), Gormle, P. Y. (Padhraig Y.), Linden, K. (Kari), Whelan, C. (Christopher), Xu, F. (Fanli), Pulford, D. (David), Frkkil, M. (Martti), Pikkarainen, S. (Sampsa), Jussila, A. (Airi), Blomster, T. (Timo), Kiviniemi, M. (Mikko), Voutilainen, M. (Markku), Georgantas, B. (Bob), Heap, G. (Graham), Rahimov, F. (Fedik), Usiskin, K. (Keith), Maranville, J. (Joseph), Lu, T. (Tim), Oh, D. (Danny), Kalpala, K. (Kirsi), Miller, M. (Melissa), McCarthy, L. (Linda), Eklund, K. (Kari), Palomki, A. (Antti), Isomki, P. (Pia), Piri, L. (Laura), Kaipiainen-Seppnen, O. (Oili), Lertratanaku, A. (Apinya), Bing, D. C. (David Close Marla Hochfeld Nan), Gordillo, J. E. (Jorge Esparza), Mars, N. (Nina), Laitinen, T. (Tarja), Pelkonen, M. (Margit), Kauppi, P. (Paula), Kankaanranta, H. (Hannu), Harju, T. (Terttu), Greenberg, S. (Steven), Chen, H. (Hubert), Betts, J. (Jo), Ghosh, S. (Soumitra), Salomaa, V. (Veikko), Niiranen, T. (Teemu), Juonala, M. (Markus), Metsrinne, K. (Kaj), Khnen, M. (Mika), Junttila, J. (Juhani), Laakso, M. (Markku), Pihlajamki, J. (Jussi), Sinisalo, J. (Juha), Taskinen, M.-R. (Marja-Riitta), Tuomi, T. (Tiinamaija), Laukkanen, J. (Jari), Challis, B. (Ben), Peterson, A. (Andrew), Chu, A. (Audrey), Parkkinen, J. (Jaakko), Muslin, A. (Anthony), Joensuu, H. (Heikki), Meretoja, T. (Tuomo), Aaltonen, L. (Lauri), Auranen, A. (Annika), Karihtala, P. (Peeter), Kauppila, S. (Saila), Auvinen, P. (Pivi), Elenius, K. (Klaus), Popovic, R. (Relja), Schutzman, J. (Jennifer), Loboda, A. (Andrey), Chhibber, A. (Aparna), Lehtonen, H. (Heli), McDonough, S. (Stefan), Crohns, M. (Marika), Kulkarni, D. (Diptee), Kaarniranta, K. (Kai), Turunen, J. (Joni), Ollila, T. (Terhi), Seitsonen, S. (Sanna), Uusitalo, H. (Hannu), Aaltonen, V. (Vesa), Uusitalo-Jrvinen, H. (Hannele), Luodonp, M. (Marja), Hautala, N. (Nina), Strauss, E. (Erich), Chen, H. (Hao), Podgornaia, A. (Anna), Hoffman, J. (Joshua), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Hannula-Jouppi, K. (Katariina), Salmi, T. (Teea), Peltonen, S. (Sirkku), Koulu, L. (Leena), Harvima, I. (Ilkka), Wu, Y. (Ying), Choy, D. (David), Jalanko, A. (Anu), Kajanne, R. (Risto), Lyhs, U. (Ulrike), Kaunisto, M. (Mari), Davis, J. W. (Justin Wade), Quarless, D. (Danjuma), Petrovski, S. (Slav), Chen, C.-Y. (Chia-Yen), Bronson, P. (Paola), Yang, R. (Robert), Chang, D. (Diana), Bhangale, T. (Tushar), Holzinger, E. (Emily), Wang, X. (Xulong), Chen, X. (Xing), Auro, K. (Kirsi), Wang, C. (Clarence), Xu, E. (Ethan), Auge, F. (Franck), Chatelain, C. (Clement), Kurki, M. (Mitja), Karjalainen, J. (Juha), Havulinna, A. (Aki), Palin, K. (Kimmo), Palta, P. (Priit), Parolo, P. D. (Pietro Della Briotta), Zhou, W. (Wei), Lemmel, S. (Susanna), Rivas, M. (Manuel), Harju, J. (Jarmo), Lehisto, A. (Arto), Ganna, A. (Andrea), Llorens, V. (Vincent), Karlsson, A. (Antti), Kristiansson, K. (Kati), Hyvrinen, K. (Kati), Ritari, J. (Jarmo), Wahlfors, T. (Tiina), Koskinen, M. (Miika), Pylkäs, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Mantere, T. (Tuomo), Kangasniemi, E. (Eeva), Heikkinen, S. (Sami), Laakkonen, E. (Eija), Kononen, J. (Juha), Loukola, A. (Anu), Laiho, P. (Pivi), Sistonen, T. (Tuuli), Kaiharju, E. (Essi), Laukkanen, M. (Markku), Jrvensivu, E. (Elina), Lhteenmki, S. (Sini), Mnnikk, L. (Lotta), Wong, R. (Regis), Mattsson, H. (Hannele), Hiekkalinna, T. (Tero), Jimnez, M. G. (Manuel Gonzlez), Donner, K. (Kati), Prn, K. (KaIle), Nunez-Fontarnau, J. (Javier), Kilpelinen, E. (Elina), Sipi, T. P. (Timo P.), Brein, G. (Georg), Dada, A. (Alexander), Awaisa, G. (Ghazal), Shcherban, A. (Anastasia), Sipil, T. (Tuomas), Laivuori, H. (Hannele), Kiiskinen, T. (Tuomo), Siirtola, H. (Harri), Tabuenca, J. G. (Javier Gracia), Kallio, L. (Lila), Soini, S. (Sirpa), Pitknen, K. (Kimmo), and Kuopio, T. (Teijo)
Subjects: Cardiovascular genetics, Genome-wide association studies
Abstract: Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
Published: 2021

5. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author: Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), Boomsma, D.I. (Dorret I.), Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), and Boomsma, D.I. (Dorret I.)
Abstract: DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48
Published: 2021
Full Text: View/download PDF

6. Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability (Nature Communications, (2021), 12, 1, (24), 10.1038/s41467-020-19366-9)

Author: Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J.L. (Josine L.), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A.J. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), Geus, E.J.C. (Eco) de, Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Matullo, G., Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth J. F.), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P. (Patricia), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Barroso, I.E. (Inês), Morris, A.P. (Andrew), Prokopenko, I. (Inga), Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J.L. (Josine L.), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A.J. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), Geus, E.J.C. (Eco) de, Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Matullo, G., Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth J. F.), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P. (Patricia), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Barroso, I.E. (Inês), Morris, A.P. (Andrew), and Prokopenko, I. (Inga)
Abstract: The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped. This has now been corrected in the PDF and HTML versions of the Article.
Published: 2021
Full Text: View/download PDF

7. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author: Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J. (Josine), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah H.), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), de Geus, E.J.C.N. (Eco J. C. N.), Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard O.), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), van Duijn, C.M. (Cornelia M.), Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy L.), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Navis, G. (Gerjan), Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P.B. (Patricia B.), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Dupuis, J. (Josée), Barroso, I.E. (Inês), Morris, A.P. (Andrew P.), Prokopenko, I. (Inga), Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J. (Josine), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah H.), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), de Geus, E.J.C.N. (Eco J. C. N.), Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard O.), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), van Duijn, C.M. (Cornelia M.), Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy L.), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Navis, G. (Gerjan), Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P.B. (Patricia B.), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Dupuis, J. (Josée), Barroso, I.E. (Inês), Morris, A.P. (Andrew P.), and Prokopenko, I. (Inga)
Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
Published: 2021
Full Text: View/download PDF

8. The power of genetic diversity in genome-wide association studies of lipids

Author: Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), Willer, C. J. (Cristen J.), Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), and Willer, C. J. (Cristen J.)
Abstract: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4‐23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.
Published: 2021

9. DNA methylation signatures of aggression and closely related constructs:a meta-analysis of epigenome-wide studies across the lifespan

Author: van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), Boomsma, D. I. (Dorret, I), van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), and Boomsma, D. I. (Dorret, I)
Abstract: DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Published: 2021

10. Polygenic burden has broader impact on health, cognition, and socioeconomic outcomes than most rare and high-risk copy number variants

Author: Saarentaus, E. C. (Elmo Christian), Havulinna, A. S. (Aki Samuli), Mars, N. (Nina), Ahola-Olli, A. (Ari), Kiiskinen, T. T. (Tuomo Tapio Johannes), Partanen, J. (Juulia), Ruotsalainen, S. (Sanni), Kurki, M. (Mitja), Urpa, L. M. (Lea Martta), Chen, L. (Lei), Perola, M. (Markus), Salomaa, V. (Veikko), Veijola, J. (Juha), Männikkö, M. (Minna), Hall, I. M. (Ira M.), Pietiläinen, O. (Olli), Kaprio, J. (Jaakko), Ripatti, S. (Samuli), Daly, M. (Mark), Palotie, A. (Aarno), Saarentaus, E. C. (Elmo Christian), Havulinna, A. S. (Aki Samuli), Mars, N. (Nina), Ahola-Olli, A. (Ari), Kiiskinen, T. T. (Tuomo Tapio Johannes), Partanen, J. (Juulia), Ruotsalainen, S. (Sanni), Kurki, M. (Mitja), Urpa, L. M. (Lea Martta), Chen, L. (Lei), Perola, M. (Markus), Salomaa, V. (Veikko), Veijola, J. (Juha), Männikkö, M. (Minna), Hall, I. M. (Ira M.), Pietiläinen, O. (Olli), Kaprio, J. (Jaakko), Ripatti, S. (Samuli), Daly, M. (Mark), and Palotie, A. (Aarno)
Abstract: Copy number variants (CNVs) are associated with syndromic and severe neurological and psychiatric disorders (SNPDs), such as intellectual disability, epilepsy, schizophrenia, and bipolar disorder. Although considered high-impact, CNVs are also observed in the general population. This presents a diagnostic challenge in evaluating their clinical significance. To estimate the phenotypic differences between CNV carriers and non-carriers regarding general health and well-being, we compared the impact of SNPD-associated CNVs on health, cognition, and socioeconomic phenotypes to the impact of three genome-wide polygenic risk score (PRS) in two Finnish cohorts (FINRISK, n = 23,053 and NFBC1966, n = 4895). The focus was on CNV carriers and PRS extremes who do not have an SNPD diagnosis. We identified high-risk CNVs (DECIPHER CNVs, risk gene deletions, or large [>1 Mb] CNVs) in 744 study participants (2.66%), 36 (4.8%) of whom had a diagnosed SNPD. In the remaining 708 unaffected carriers, we observed lower educational attainment (EA; OR = 0.77 [95% CI 0.66–0.89]) and lower household income (OR = 0.77 [0.66–0.89]). Income-associated CNVs also lowered household income (OR = 0.50 [0.38–0.66]), and CNVs with medical consequences lowered subjective health (OR = 0.48 [0.32–0.72]). The impact of PRSs was broader. At the lowest extreme of PRS for EA, we observed lower EA (OR = 0.31 [0.26–0.37]), lower-income (OR = 0.66 [0.57–0.77]), lower subjective health (OR = 0.72 [0.61–0.83]), and increased mortality (Cox’s HR = 1.55 [1.21–1.98]). PRS for intelligence had a similar impact, whereas PRS for schizophrenia did not affect these traits. We conclude that the majority of working-age individuals carrying high-risk CNVs without SNPD diagnosis have a modest impact on morbidity and mortality, as well as the limited impact on income and educational attainment, compared to individuals at the extreme end of common genetic variation. Our findings highlight that the contribution of trad
Published: 2021

11. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), Debette, S. (Stéphanie), Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), and Debette, S. (Stéphanie)
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020
Full Text: View/download PDF

12. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Author: Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), Chasman, D.I. (Daniel), Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), and Chasman, D.I. (Daniel)
Abstract: Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
Published: 2020
Full Text: View/download PDF

13. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author: Fan, Q. (Qiao), Pozarickij, A. (Alfred), Tan, N.Y.Q. (Nicholas Y. Q.), Guo, X. (Xiaobo), Verhoeven, V.J.M. (Virginie), Vitart, V. (Veronique), Guggenheim, J. (Jean), Miyake, M. (Masahiro), Tideman, J.W.L. (Willem), Khawaja, A.P. (Anthony), Zhang, L. (Liang), MacGregor, S. (Stuart), Höhn, R. (René), Chen, P. (Peng), Biino, G. (Ginevra), Wedenoja, J. (Juho), Saffari, S.E. (Seyed Ehsan), Tedja, M. (Milly), Xie, J. (Jing), Lanca, C. (Carla), Wang, Y.X. (Ya Xing), Sahebjada, S. (Srujana), Mazur, J. (Johanna), Mirshahi, A. (Alireza), Martin, N.G. (Nicholas), Yazar, S. (Seyhan), Pennell, C.E. (Craig), Yap, M.K.H. (Maurice K. H.), Haarman, A.E.G. (Annechien E. G.), Enthoven, C.A. (Clair A.), Polling, J.R. (Jan Roelof), Bailey-Wilson, J.E. (Joan E.), Veluchamy, A.B. (Amutha Barathi), Burdon, K.P. (Kathryn P.), Campbell, H. (Harry), Chen, L.J. (Li Jia), Chew, E.Y. (Emily Y.), Craig, J.E. (Jamie), Cumberland, P.M. (Phillippa M.), DeAngelis, M.M. (Margaret), Delcourt, C. (Cécile), Ding, X. (Xiaohu), Evans, D.M. (David M.), Gharahkhani, P. (Puya), Iglesias, A.I. (Adriana I.), Haller, T. (Toomas), Han, X. (Xikun), Hoang, Q. (Quan), Igo Jr., R.P. (Robert), Iyengar, S.K. (Sudha), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Klein, B.E. (Barbara E.), Klein, R. (Ronald), Lass Jr., J.H. (Jonathan), Lee, K. (Kris), Lehtimäki, T. (Terho), Lewis, D.D. (Deyana D.), Li, Q. (Qing), Li, S.-M. (Shi-Ming), Lyytikäinen, L.-P. (Leo-Pekka), Meguro, A. (Akira), Metspalu, A. (Andres), Middlebrooks, C.D. (Candace D.), Mizuki, N. (Nobuhisa), Musolf, A.M. (Anthony M.), Nickels, S. (Stefan), Oexle, K. (Konrad), Pang, C.P. (Chi Pui), Paterson, A.D. (Andrew), Rahi, J.S. (Jugnoo S.), Raitakari, O. (Olli), Rudan, I. (Igor), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wang, N. (Ningli), Bin Wei, W. (Wen), Williams, K.M. (Katie M.), Wilson, J.F. (James), Wojciechowski, R. (Robert), Yamashiro, K. (Kenji), Yam, J.C.S. (Jason C. S.), Zhou, X. (Xiangtian), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jenny H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Fruttiger, M. (Marcus), Gallacher, J. (John), Garway-Heath, D.F. (David F.), Gibson, J. (Jane), Gore, D. (Dan), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, S.P.T. (Sir Peng T.), Lascaratos, G. (Gerassimos), Lotery, A.J. (Andrew), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Viswanathan, A.C. (Ananth C.), Williams, K. (Katie), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Hewit, A.W. (Alex), Jaddoe, V.W.V. (Vincent), Duijn, C.M. (Cornelia) van, Hayward, C. (Caroline), Polasek, O. (Ozren), Tai, E.S. (Shyong), Yoshikatsu, H. (Hosoda), Hysi, P.G. (Pirro G.), Young, T.L. (Terri L.), Tsujikawa, A. (Akitaka), Wang, J.J. (Jie Jing), Mitchell, P. (Paul), Pfeiffer, A.F.H. (Andreas), Pärssinen, O. (Olavi), Foster, P.J. (Paul), Fossarello, M. (Maurizio), Yip, S.P. (Shea Ping), Williams, C. (Cathy), Hammond, C.J. (Christopher), Jonas, J.B., He, M. (Mingguang), Mackey, D.A. (David), Wong, T.-Y. (Tien-Yin), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Baird, P.N. (Paul), Cheng, C.-Y. (Ching-Yu), Fan, Q. (Qiao), Pozarickij, A. (Alfred), Tan, N.Y.Q. (Nicholas Y. Q.), Guo, X. (Xiaobo), Verhoeven, V.J.M. (Virginie), Vitart, V. (Veronique), Guggenheim, J. (Jean), Miyake, M. (Masahiro), Tideman, J.W.L. (Willem), Khawaja, A.P. (Anthony), Zhang, L. (Liang), MacGregor, S. (Stuart), Höhn, R. (René), Chen, P. (Peng), Biino, G. (Ginevra), Wedenoja, J. (Juho), Saffari, S.E. (Seyed Ehsan), Tedja, M. (Milly), Xie, J. (Jing), Lanca, C. (Carla), Wang, Y.X. (Ya Xing), Sahebjada, S. (Srujana), Mazur, J. (Johanna), Mirshahi, A. (Alireza), Martin, N.G. (Nicholas), Yazar, S. (Seyhan), Pennell, C.E. (Craig), Yap, M.K.H. (Maurice K. H.), Haarman, A.E.G. (Annechien E. G.), Enthoven, C.A. (Clair A.), Polling, J.R. (Jan Roelof), Bailey-Wilson, J.E. (Joan E.), Veluchamy, A.B. (Amutha Barathi), Burdon, K.P. (Kathryn P.), Campbell, H. (Harry), Chen, L.J. (Li Jia), Chew, E.Y. (Emily Y.), Craig, J.E. (Jamie), Cumberland, P.M. (Phillippa M.), DeAngelis, M.M. (Margaret), Delcourt, C. (Cécile), Ding, X. (Xiaohu), Evans, D.M. (David M.), Gharahkhani, P. (Puya), Iglesias, A.I. (Adriana I.), Haller, T. (Toomas), Han, X. (Xikun), Hoang, Q. (Quan), Igo Jr., R.P. (Robert), Iyengar, S.K. (Sudha), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Klein, B.E. (Barbara E.), Klein, R. (Ronald), Lass Jr., J.H. (Jonathan), Lee, K. (Kris), Lehtimäki, T. (Terho), Lewis, D.D. (Deyana D.), Li, Q. (Qing), Li, S.-M. (Shi-Ming), Lyytikäinen, L.-P. (Leo-Pekka), Meguro, A. (Akira), Metspalu, A. (Andres), Middlebrooks, C.D. (Candace D.), Mizuki, N. (Nobuhisa), Musolf, A.M. (Anthony M.), Nickels, S. (Stefan), Oexle, K. (Konrad), Pang, C.P. (Chi Pui), Paterson, A.D. (Andrew), Rahi, J.S. (Jugnoo S.), Raitakari, O. (Olli), Rudan, I. (Igor), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wang, N. (Ningli), Bin Wei, W. (Wen), Williams, K.M. (Katie M.), Wilson, J.F. (James), Wojciechowski, R. (Robert), Yamashiro, K. (Kenji), Yam, J.C.S. (Jason C. S.), Zhou, X. (Xiangtian), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jenny H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Fruttiger, M. (Marcus), Gallacher, J. (John), Garway-Heath, D.F. (David F.), Gibson, J. (Jane), Gore, D. (Dan), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, S.P.T. (Sir Peng T.), Lascaratos, G. (Gerassimos), Lotery, A.J. (Andrew), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Viswanathan, A.C. (Ananth C.), Williams, K. (Katie), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Hewit, A.W. (Alex), Jaddoe, V.W.V. (Vincent), Duijn, C.M. (Cornelia) van, Hayward, C. (Caroline), Polasek, O. (Ozren), Tai, E.S. (Shyong), Yoshikatsu, H. (Hosoda), Hysi, P.G. (Pirro G.), Young, T.L. (Terri L.), Tsujikawa, A. (Akitaka), Wang, J.J. (Jie Jing), Mitchell, P. (Paul), Pfeiffer, A.F.H. (Andreas), Pärssinen, O. (Olavi), Foster, P.J. (Paul), Fossarello, M. (Maurizio), Yip, S.P. (Shea Ping), Williams, C. (Cathy), Hammond, C.J. (Christopher), Jonas, J.B., He, M. (Mingguang), Mackey, D.A. (David), Wong, T.-Y. (Tien-Yin), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Baird, P.N. (Paul), and Cheng, C.-Y. (Ching-Yu)
Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.
Published: 2020
Full Text: View/download PDF

14. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), Codd, V. (Veryan), Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), and Codd, V. (Veryan)
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020
Full Text: View/download PDF

15. The role of polygenic risk and susceptibility genes in breast cancer over the course of life

Author: Mars, N. (Nina), Widén, E. (Elisabeth), Kerminen, S. (Sini), Meretoja, T. (Tuomo), Pirinen, M. (Matti), della Briotta Parolo, P. (Pietro), Palta, P. (Priit), . (), Palotie, A. (Aarno), Kaprio, J. (Jaakko), Joensuu, H. (Heikki), Daly, M. (Mark), Ripatti, S. (Samuli), Mars, N. (Nina), Widén, E. (Elisabeth), Kerminen, S. (Sini), Meretoja, T. (Tuomo), Pirinen, M. (Matti), della Briotta Parolo, P. (Pietro), Palta, P. (Priit), . (), Palotie, A. (Aarno), Kaprio, J. (Jaakko), Joensuu, H. (Heikki), Daly, M. (Mark), and Ripatti, S. (Samuli)
Abstract: Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10–90th percentile) have a lifetime risk of breast cancer at 55% (95% CI 49–61%), which increases to 84% (71–97%) with a high PRS ( > 90th percentile), and decreases to 49% (30–68%) with a low PRS ( < 10th percentile). Similarly, for c.1100delC in CHEK2 (3.7–fold enrichment; 1648 carriers), the respective lifetime risks are 29% (27–32%), 59% (52–66%), and 9% (5–14%). The PRS also refines the risk assessment of women with first-degree relatives diagnosed with breast cancer, particularly among women with positive family history of early-onset breast cancer. Here we demonstrate the opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members., FinnGen Aarno Palotie1,7,8, Aki Havulinna1, Amanda Elliott1,8, Anastasia Shcherban1, Andrea Ganna1, Anu Jalanko1, Arto Lehisto1, Elina Kilpeläinen1, Georg Brein1, Ghazal Awaisa1, Hannele Laivuori1, Henrike Heyne1, Jaakko Kaprio1,5, Jarmo Harju1, Jiwoo Lee1,8, Juha Karjalainen1,8, Jukka Koskela1, Kalle Pärn1, Kati Donner1, Kristin Tsuo1,8, Manuel González Jiménez1, Mark Daly1,8, Mari Kaunisto1, Mari E. Niemi1, Mary Pat Reeve1, Mervi Aavikko1, Mitja Kurki1,8, Nina Mars1, Oluwaseun A. Dada1, Pietro della Briotta Parolo1, Priit Palta1,6, Risto Kajanne1, Samuli Ripatti1,6,8, Sina Rüeger1, Susanna Lemmelä1, Taru Tukiainen1, Tiinamaija Tuomi1, Timo P. Sipilä1, Tuomo Kiiskinen1, Vincent Llorens1, Adam Ziemann10, Anne Lehtonen10, Apinya Lertratanakul10, Bob Georgantas10, Bridget Riley-Gillis10, Danjuma Quarless10, Fedik Rahimov10, Howard Jacob10, Jeffrey Waring10, Justin Wade Davis10, Nizar Smaoui10, Relja Popovic10, Sahar Esmaeeli10, Athena Matakidou11, Ben Challis11, David Close11, Eleonor Wigmore11, Slavé Petrovski11, Chia-Yen Chen12, Ellen Tsai12, Heiko Runz12, Jimmy Liu12, Paola Bronson12, Sally John12, Sanni Lahdenperä12, Stephanie Loomis12, Susan Eaton12, Yunfeng Huang12, Erika Kvikstad13, Minal Caliskan13, Samir Wadhawan13, Elmutaz Shaikho Elhaj Mohammed14, Janet van Adelsberg14, Joseph Maranville14, Marla Hochfeld14, Robert Plenge14, Shameek Biswas14, Steven Greenberg14, Andrew Peterson15, David Choy15, Diana Chang15, Edmond Teng15, Erich Strauss15, Geoff Kerchner15, Hao Chen15, Hubert Chen15, Jennifer Schutzman15, John Michon15, Julie Hunkapiller15, Mark McCarthy15, Natalie Bowers15, Sarah Pendergrass15, Tushar Bhangale15, David Pulford16, Dawn Waterworth16, Diptee Kulkarni16, Fanli Xu16, Jo Betts16, Jorge Esparza Gordillo16, Joshua Hoffman16, Karen S. King16, Meg Ehm16, Soumitra Ghosh16, Patrick Loerch17, Wilco Fleuren17, Beryl Cummings18, Matt Brauer18, Robert Graham18, Tim Behrens18, Andrey Loboda19, Anna Podgornaia19, Aparna Chhibber19, Audrey Chu19, Caroline F
Published: 2020

16. Polygenic risk scores and physical activity

Author: Kujala, U. M. (Urho M.), Palviainen, T. (Teemu), Pesonen, P. (Paula), Waller, K. (Katja), Sillanpää, E. (Elina), Niemelä, M. (Maisa), Kangas, M. (Maarit), Vähä-Ypyä, H. (Henri), Sievänen, H. (Harri), Korpelainen, R. (Raija), Jämsä, T. (Timo), Männikkö, M. (Minna), Kaprio, J. (Jaakko), Kujala, U. M. (Urho M.), Palviainen, T. (Teemu), Pesonen, P. (Paula), Waller, K. (Katja), Sillanpää, E. (Elina), Niemelä, M. (Maisa), Kangas, M. (Maarit), Vähä-Ypyä, H. (Henri), Sievänen, H. (Harri), Korpelainen, R. (Raija), Jämsä, T. (Timo), Männikkö, M. (Minna), and Kaprio, J. (Jaakko)
Abstract: Purpose: Polygenic risk scores (PRS) summarize genome-wide genotype data into a single variable that produces an individual-level risk score for genetic liability. PRS has been used for prediction of chronic diseases and some risk factors. As PRS has been studied less for physical activity (PA), we constructed PRS for PA and studied how much variation in PA can be explained by this PRS in independent population samples. Methods: We calculated PRS for self-reported and objectively measured PA using UK Biobank genome-wide association study summary statistics, and analyzed how much of the variation in self-reported (MET-hours per day) and measured (steps and moderate-to-vigorous PA minutes per day) PA could be accounted for by the PRS in the Finnish Twin Cohorts (FTC; N = 759–11,528) and the Northern Finland Birth Cohort 1966 (NFBC1966; N = 3263–4061). Objective measurement of PA was done with wrist-worn accelerometer in UK Biobank and NFBC1966 studies, and with hip-worn accelerometer in the FTC. Results: The PRS accounted from 0.07% to 1.44% of the variation (R2) in the self-reported and objectively measured PA volumes (P value range = 0.023 to <0.0001) in the FTC and NFBC1966. For both self-reported and objectively measured PA, individuals in the highest PRS deciles had significantly (11%–28%) higher PA volumes compared with the lowest PRS deciles (P value range = 0.017 to <0.0001). Conclusions: PA is a multifactorial phenotype, and the PRS constructed based on UK Biobank results accounted for statistically significant but overall small proportion of the variation in PA in the Finnish cohorts. Using identical methods to assess PA and including less common and rare variants in the construction of PRS may increase the proportion of PA explained by the PRS.
Published: 2020

17. Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Author: Tabassum, R. (Rubina), Ramo, J. T. (Joel T.), Ripatti, P. (Pietari), Koskela, J. T. (Jukka T.), Kurki, M. (Mitja), Karjalainen, J. (Juha), Palta, P. (Priit), Hassan, S. (Shabbeer), Nunez-Fontarnau, J. (Javier), Kiiskinen, T. T. (Tuomo T. J.), Soderlund, S. (Sanni), Matikainen, N. (Niina), Gerl, M. J. (Mathias J.), Surma, M. A. (Michal A.), Klose, C. (Christian), Stitziel, N. O. (Nathan O.), Laivuori, H. (Hannele), Havulinna, A. S. (Aki S.), Service, S. K. (Susan K.), Salomaa, V. (Veikko), Pirinen, M. (Matti), Jauhiainen, M. (Matti), Daly, M. J. (Mark J.), Freimer, N. B. (Nelson B.), Palotie, A. (Aarno), Taskinen, M.-R. (Marja-Riitta), Simons, K. (Kai), Ripatti, S. (Samuli), Jalanko, A. (Anu), Kaprio, J. (Jaakko), Donner, K. (Kati), Kaunisto, M. (Mari), Mars, N. (Nina), Dada, A. (Alexander), Shcherban, A. (Anastasia), Ganna, A. (Andrea), Lehisto, A. (Arto), Kilpelainen, E. (Elina), Brein, G. (Georg), Awaisa, G. (Ghazal), Harju, J. (Jarmo), Parr, K. (Kalle), Parolo, P. D. (Pietro Della Briotta), Kajanne, R. (Risto), Lemmela, S. (Susanna), Sipila, T. P. (Timo P.), Sipila, T. (Tuomas), Lyhs, U. (Ulrike), Llorens, V. (Vincent), Niiranen, T. (Teemu), Kristiansson, K. (Kati), Mannikko, L. (Lotta), Jimenez, M. G. (Manuel Gonzalez), Perola, M. (Markus), Wong, R. (Regis), Kilpi, T. (Terhi), Hiekkalinna, T. (Tero), Jarvensivu, E. (Elina), Kaiharju, E. (Essi), Mattsson, H. (Hannele), Laukkanen, M. (Markku), Laiho, P. (Paivi), Lahteenmaki, S. (Sini), Sistonen, T. (Tuuli), Soini, S. (Sirpa), Ziemann, A. (Adam), Lehtonen, A. (Anne), Lertratanakul, A. (Apinya), Georgantas, B. (Bob), Riley-Gillis, B. (Bridget), Quarless, D. (Danjuma), Rahimov, F. (Fedik), Heap, G. (Graham), Jacob, H. (Howard), Waring, J. (Jeffrey), Davis, J. W. (Justin Wade), Smaoui, N. (Nizar), Popovic, R. (Relja), Esmaeeli, S. (Sahar), Waring, J. (Jeff), Matakidou, A. (Athena), Challis, B. (Ben), Close, D. (David), Petrovski, S. (Slave), Karlsson, A. (Antti), Schleutker, J. (Johanna), Pulkki, K. (Kari), Virolainen, P. (Petri), Kallio, L. (Lila), Mannermaa, A. (Arto), Heikkinen, S. (Sami), Kosma, V.-M. (Veli-Matti), Chen, C.-Y. (Chia-Yen), Runz, H. (Heiko), Liu, J. (Jimmy), Bronson, P. (Paola), John, S. (Sally), Landenpera, S. (Sanni), Eaton, S. (Susan), Zhou, W. (Wei), Hendolin, M. (Minna), Tuovila, O. (Outi), Pakkanen, R. (Raimo), Maranville, J. (Joseph), Usiskin, K. (Keith), Hochfeld, M. (Marla), Plenge, R. (Robert), Yang, R. (Robert), Biswas, S. (Shameek), Greenberg, S. (Steven), Laakkonen, E. (Eija), Kononen, J. (Juha), Paloneva, J. (Juha), Kujala, U. (Urho), Kuopio, T. (Teijo), Laukkanen, J. (Jari), Kangasniemi, E. (Eeva), Savinainen, K. (Kimmo), Laaksonen, R. (Reijo), Arvas, M. (Mikko), Ritari, J. (Jarmo), Partanen, J. (Jukka), Hyvarinen, K. (Kati), Wahlfors, T. (Tiina), Peterson, A. (Andrew), Oh, D. (Danny), Chang, D. (Diana), Teng, E. (Edmond), Strauss, E. (Erich), Kerchner, G. (Geoff), Chen, H. (Hao), Chen, H. (Hubert), Schutzman, J. (Jennifer), Michon, J. (John), Hunkapiller, J. (Julie), McCarthy, M. (Mark), Bowers, N. (Natalie), Lu, T. (Tim), Bhangale, T. (Tushar), Pulford, D. (David), Waterworth, D. (Dawn), Kulkarni, D. (Diptee), Xu, F. (Fanli), Betts, J. (Jo), Gordillo, J. E. (Jorge Esparza), Hoffman, J. (Joshua), Auro, K. (Kirsi), McCarthy, L. (Linda), Ghosh, S. (Soumitra), Ehm, M. (Meg), Pitkanen, K. (Kimmo), Makela, T. (Tomi), Loukola, A. (Anu), Joensuu, H. (Heikki), Sinisalo, J. (Juha), Eklund, K. (Kari), Aaltonen, L. (Lauri), Farkkila, M. (Martti), Carpen, O. (Olli), Kauppi, P. (Paula), Tienari, P. (Pentti), Ollila, T. (Terhi), Tuomi, T. (Tiinamaija), Meretoja, T. (Tuomo), Pitkaranta, A. (Anne), Turunen, J. (Joni), Hannula-Jouppi, K. (Katariina), Pikkarainen, S. (Sampsa), Seitsonen, S. (Sanna), Koskinen, M. (Miika), Palomaki, A. (Antti), Rinne, J. (Juha), Metsarinne, K. (Kaj), Elenius, K. (Klaus), Pirila, L. (Laura), Koulu, L. (Leena), Voutilainen, M. (Markku), Juonala, M. (Markus), Peltonen, S. (Sirkku), Aaltonen, V. (Vesa), Loboda, A. (Andrey), Podgornaia, A. (Anna), Chhibber, A. (Aparna), Chu, A. (Audrey), Fox, C. (Caroline), Diogo, D. (Dorothee), Holzinger, E. (Emily), Eicher, J. (John), Gormley, P. (Padhraig), Mehta, V. (Vinay), Wang, X. (Xulong), Kettunen, J. (Johannes), Pylkas, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Hinttala, R. (Reetta), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Mantere, T. (Tuomo), Remes, A. (Anne), Huhtakangas, J. (Johanna), Junttila, J. (Juhani), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Luodonpaa, M. (Marja), Hautala, N. (Nina), Karihtala, P. (Peeter), Kauppila, S. (Saila), Harju, T. (Terttu), Blomster, T. (Timo), Soininen, H. (Hilkka), Harvima, I. (Ilkka), Pihlajamaki, J. (Jussi), Kaarniranta, K. (Kai), Pelkonen, M. (Margit), Laakso, M. (Markku), Hiltunen, M. (Mikko), Kiviniemi, M. (Mikko), Kaipiainen-Seppanen, O. (Oili), Auvinen, P. (Paivi), Kalviainen, R. (Reetta), Julkunen, V. (Valtteri), Malarstig, A. (Anders), Hedman, A. (Asa), Marshal, C. (Catherine), Whelan, C. (Christopher), Lehtonen, H. (Heli), Parkkinen, J. (Jaakko), Linden, K. (Kari), Kalpala, K. (Kirsi), Miller, M. (Melissa), Bing, N. (Nan), McDonough, S. (Stefan), Chen, X. (Xing), Hu, X. (Xinli), Wu, Y. (Ying), Auranen, A. (Annika), Jussila, A. (Airi), Uusitalo-Jarvinen, H. (Hannele), Kankaanranta, H. (Hannu), Uusitalo, H. (Hannu), Peltola, J. (Jukka), Kahonen, M. (Mika), Isomaki, P. (Pia), Laitinen, T. (Tarja), Salmi, T. (Teea), Muslin, A. (Anthony), Wang, C. (Clarence), Chatelain, C. (Clement), Xu, E. (Ethan), Auge, F. (Franck), Call, K. (Kathy), Klinger, K. (Kathy), Crohns, M. (Marika), Gossel, M. (Matthias), Palin, K. (Kimmo), Rivas, M. (Manuel), Siirtola, H. (Harri), and Tabuenca, J. G. (Javier Gracia)
Subjects: lipids (amino acids, peptides, and proteins)
Abstract: Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P
Published: 2019

18. Associations of autozygosity with a broad range of human phenotypes

Author: Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), Wilson, J.F. (James), Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), and Wilson, J.F. (James)
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
Published: 2019
Full Text: View/download PDF

19. Correction: Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation (Molecular Psychiatry, (2018), 10.1038/s41380-018-0112-7)

Author: Bis, J.C. (Joshua), Jian, X. (Xueqiu), Kunkle, B.W. (Brian W.), Chen, Y. (Yuning), Hamilton-Nelson, K.L. (Kara L.), Bush, W.S. (William S.), Salerno, W.J. (William J.), Lancour, D. (Daniel), Ma, Y. (Yiyi), Renton, A. (Alan), Marcora, E. (Edoardo), Farrell, J.J. (John J.), Zhao, Y. (Yi), Qu, L. (Liming), Ahmad, S. (Shahzad), Amin, N. (Najaf), Amouyel, P. (Philippe), Beecham, G.W., Below, J.E. (Jennifer E.), Campion, D. (Dominique), Cantwell, L.B. (Laura B.), Charbonnier, C. (Camille), Chung, J. (Jaeyoon), Crane, P.K. (Paul K.), Crane, L.M.A., Cupples, L.A. (L. Adrienne), Dartigues, J.-F., Debette, S. (Stéphanie), Deleuze, J.-F. (Jean-François), Fulton, L. (Lucinda), Gabriel, S.B. (Stacey), Genin, E. (Emmanuelle), Gibbs, R.A. (Richard), Goate, A. (Alison), Grenier-Boley, B. (Benjamin), Gupta, N. (Namrata), Haines, J.L. (Jonathan), Havulinna, A.S. (Aki), Helisalmi, S. (Seppo), Hiltunen, M. (Mikko), Howrigan, D.P. (Daniel P.), Ikram, M.A. (Arfan), Kaprio, J. (Jaakko), Konrad, J. (Jan), Kuzma, A. (Amanda), Lander, E.S. (Eric), Lathrop, M. (Mark), Lehtimäki, T. (Terho), Lin, H. (Honghuang), Mattila, K. (Kari), Mayeux, R. (Richard), Muzny, D. (Donna), Nasser, W. (Waleed), Neale, B.M. (Benjamin), Nho, K. (Kwangsik), Nicolas, G. (Gaël), Patel, D. (Devanshi), Kunkle, B. (Brian), Perola, M. (Markus), Psaty, B.M. (Bruce), Quenez, O. (Olivier), Rajabli, F. (Farid), Redon, R. (Richard), Reitz, C. (Christiane), Remes, A. (Anne), Salomaa, V. (Veikko), Sarnowski, C., Schmidt, H. (Helena), Schmidt, M. (Michael), Schmidt, R. (Reinhold), Soininen, H. (H.), Thornton, T.A. (Timothy A.), Tosto, G. (G.), Tzourio, C. (Christophe), Lee, S.J. (Sven) van der, Duijn, C.M. (Cornelia) van, Valladares, O. (Otto), Vardarajan, B.N. (Badri), Wang, L.S. (Li-San), Wang, W. (Weixin), Wijsman, E. (Ellen), Wilson, R.K. (Richard K.), Witten, D. (Daniela), Worley, K.C. (Kim C.), Zhang, X. (Xiaoling), Bellenguez, C. (Céline), Lambert, J.-C. (J.), Kurki, M.I. (Mitja I.), Palotie, A. (Aarno), Daly, M.J. (Mark), Boerwinkle, E.A. (Eric), Lunetta, K.L. (Kathryn), DeStefano, A.L. (Anita), Martin, E.R., Schellenberg, G.D. (Gerard), Seshadri, S. (Sudha), Naj, A.C. (Adam C.), Fornage, M. (Myriam), Farrer, L.A. (Lindsay), Bis, J.C. (Joshua), Jian, X. (Xueqiu), Kunkle, B.W. (Brian W.), Chen, Y. (Yuning), Hamilton-Nelson, K.L. (Kara L.), Bush, W.S. (William S.), Salerno, W.J. (William J.), Lancour, D. (Daniel), Ma, Y. (Yiyi), Renton, A. (Alan), Marcora, E. (Edoardo), Farrell, J.J. (John J.), Zhao, Y. (Yi), Qu, L. (Liming), Ahmad, S. (Shahzad), Amin, N. (Najaf), Amouyel, P. (Philippe), Beecham, G.W., Below, J.E. (Jennifer E.), Campion, D. (Dominique), Cantwell, L.B. (Laura B.), Charbonnier, C. (Camille), Chung, J. (Jaeyoon), Crane, P.K. (Paul K.), Crane, L.M.A., Cupples, L.A. (L. Adrienne), Dartigues, J.-F., Debette, S. (Stéphanie), Deleuze, J.-F. (Jean-François), Fulton, L. (Lucinda), Gabriel, S.B. (Stacey), Genin, E. (Emmanuelle), Gibbs, R.A. (Richard), Goate, A. (Alison), Grenier-Boley, B. (Benjamin), Gupta, N. (Namrata), Haines, J.L. (Jonathan), Havulinna, A.S. (Aki), Helisalmi, S. (Seppo), Hiltunen, M. (Mikko), Howrigan, D.P. (Daniel P.), Ikram, M.A. (Arfan), Kaprio, J. (Jaakko), Konrad, J. (Jan), Kuzma, A. (Amanda), Lander, E.S. (Eric), Lathrop, M. (Mark), Lehtimäki, T. (Terho), Lin, H. (Honghuang), Mattila, K. (Kari), Mayeux, R. (Richard), Muzny, D. (Donna), Nasser, W. (Waleed), Neale, B.M. (Benjamin), Nho, K. (Kwangsik), Nicolas, G. (Gaël), Patel, D. (Devanshi), Kunkle, B. (Brian), Perola, M. (Markus), Psaty, B.M. (Bruce), Quenez, O. (Olivier), Rajabli, F. (Farid), Redon, R. (Richard), Reitz, C. (Christiane), Remes, A. (Anne), Salomaa, V. (Veikko), Sarnowski, C., Schmidt, H. (Helena), Schmidt, M. (Michael), Schmidt, R. (Reinhold), Soininen, H. (H.), Thornton, T.A. (Timothy A.), Tosto, G. (G.), Tzourio, C. (Christophe), Lee, S.J. (Sven) van der, Duijn, C.M. (Cornelia) van, Valladares, O. (Otto), Vardarajan, B.N. (Badri), Wang, L.S. (Li-San), Wang, W. (Weixin), Wijsman, E. (Ellen), Wilson, R.K. (Richard K.), Witten, D. (Daniela), Worley, K.C. (Kim C.), Zhang, X. (Xiaoling), Bellenguez, C. (Céline), Lambert, J.-C. (J.), Kurki, M.I. (Mitja I.), Palotie, A. (Aarno), Daly, M.J. (Mark), Boerwinkle, E.A. (Eric), Lunetta, K.L. (Kathryn), DeStefano, A.L. (Anita), Martin, E.R., Schellenberg, G.D. (Gerard), Seshadri, S. (Sudha), Naj, A.C. (Adam C.), Fornage, M. (Myriam), and Farrer, L.A. (Lindsay)
Abstract: Following publication, the authors noticed that ‘Laura Cantwell’, ‘Otto Valladares’, and ‘Li-San Wang’ were inadvertently omitted from the author list. These authors have now been added to the author list in 21st, 77th, and 79th position, respectively. This has been corrected in both the PDF and HTML versions of the article.
Published: 2019
Full Text: View/download PDF

20. Associations of autozygosity with a broad range of human phenotypes

Author: Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), Wilson, J. F. (James F.), Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), and Wilson, J. F. (James F.)
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
Published: 2019

21. Migraine polygenic risk score associates with efficacy of migraine-specific drugs

Author: Kogelman, L. J. (Lisette J. A.), Esserlind, A.-L. (Ann-Louise), Christensen, A. F. (Anne Francke), Awasthi, S. (Swapnil), Ripke, S. (Stephan), Ingason, A. (Andres), Davidsson, O. B. (Olafur B.), Erikstrup, C. (Christian), Hjalgrim, H. (Henrik), Ullum, H. (Henrik), Olesen, J. (Jes), Hansen, T. F. (Thomas Folkmann), Gudbjartsson, D. (Daniel), Gastafsson, O. (Omar), Stefansson, K. (Kari), Stefansson, H. (Hreinn), Porsteinsdottir, U. (Unnur), Andersen, S. (Steffen), Banasik, K. (Karina), Brunak, S. (Soren), Buil, A. (Alfonso), Burgdorf, K. (Kristoffer), Gregor, J. (Jemec), Jennum, P. (Poul), Nielsen, K. R. (Kasper Rene), Nyegaard, M. (Mette), Paarup, H. M. (Helene Mariana), Pedersen, O. B. (Ole Birger), Sorensen, E. (Erik), Werge, T. (Thomas), Anttila, V. (Verneri), Artto, V. (Ville), Belin, A. C. (Andrea Carmine), de Boer, I. (Irene), Boomsma, D. I. (Dorret, I), Borte, S. (Sigrid), Chasman, D. I. (Daniel, I), Cherkas, L. (Lynn), Cormand, B. (Bru), Cuenca-Leon, E. (Ester), Davey-Smith, G. (George), Dichgans, M. (Martin), van Duijn, C. (Cornelia), Esko, T. (Tonu), Ferrari, M. (Michel), Frants, R. R. (Rune R.), Freilinger, T. (Tobias), Furlotte, N. (Nick), Gormley, P. (Padhraig), Griffiths, L. (Lyn), Hamalainen, E. (Eija), Hiekkala, M. (Marjo), Ikram, M. A. (M. Arfan), Järvelin, M.-R. (Marjo-Riitta), Kajanne, R. (Risto), Kallela, M. (Mikko), Kaprio, J. (Jaakko), Kaunisto, M. (Mari), Kubisch, C. (Christian), Kurki, M. (Mitja), Kurth, T. (Tobias), Launer, L. (Lenore), Lehtimaki, T. (Terho), Lessel, D. (Davor), Ligthart, L. (Lannie), Litterman, N. (Nadia), van den Maagdenberg, A. (Arn), Macaya, A. (Alfons), Malik, R. (Rainer), Mangino, M. (Massimo), McMahon, G. (George), Muller-Myhsok, B. (Bertram), Neale, B. M. (Benjamin M.), Northover, C. (Carrie), Nyholt, D. R. (Dale R.), Palotie, A. (Aarno), Palta, P. (Priit), Pedersen, L. (Linda), Pedersen, N. (Nancy), Posthuma, D. (Danielle), Pozo-Rosich, P. (Patricia), Pressman, A. (Alice), Raitakari, O. (Olli), Schurks, M. (Markus), Sintas, C. (Celia), Steinberg, S. (Stacy), Strachan, D. (David), Terwindt, G. (Gisela), Vila-Pueyo, M. (Marta), Wessman, M. (Maija), Winsvold, B. S. (Bendik S.), Zhao, H. (Huiying), Zwart, J.-A. (John-Anker), Kogelman, L. J. (Lisette J. A.), Esserlind, A.-L. (Ann-Louise), Christensen, A. F. (Anne Francke), Awasthi, S. (Swapnil), Ripke, S. (Stephan), Ingason, A. (Andres), Davidsson, O. B. (Olafur B.), Erikstrup, C. (Christian), Hjalgrim, H. (Henrik), Ullum, H. (Henrik), Olesen, J. (Jes), Hansen, T. F. (Thomas Folkmann), Gudbjartsson, D. (Daniel), Gastafsson, O. (Omar), Stefansson, K. (Kari), Stefansson, H. (Hreinn), Porsteinsdottir, U. (Unnur), Andersen, S. (Steffen), Banasik, K. (Karina), Brunak, S. (Soren), Buil, A. (Alfonso), Burgdorf, K. (Kristoffer), Gregor, J. (Jemec), Jennum, P. (Poul), Nielsen, K. R. (Kasper Rene), Nyegaard, M. (Mette), Paarup, H. M. (Helene Mariana), Pedersen, O. B. (Ole Birger), Sorensen, E. (Erik), Werge, T. (Thomas), Anttila, V. (Verneri), Artto, V. (Ville), Belin, A. C. (Andrea Carmine), de Boer, I. (Irene), Boomsma, D. I. (Dorret, I), Borte, S. (Sigrid), Chasman, D. I. (Daniel, I), Cherkas, L. (Lynn), Cormand, B. (Bru), Cuenca-Leon, E. (Ester), Davey-Smith, G. (George), Dichgans, M. (Martin), van Duijn, C. (Cornelia), Esko, T. (Tonu), Ferrari, M. (Michel), Frants, R. R. (Rune R.), Freilinger, T. (Tobias), Furlotte, N. (Nick), Gormley, P. (Padhraig), Griffiths, L. (Lyn), Hamalainen, E. (Eija), Hiekkala, M. (Marjo), Ikram, M. A. (M. Arfan), Järvelin, M.-R. (Marjo-Riitta), Kajanne, R. (Risto), Kallela, M. (Mikko), Kaprio, J. (Jaakko), Kaunisto, M. (Mari), Kubisch, C. (Christian), Kurki, M. (Mitja), Kurth, T. (Tobias), Launer, L. (Lenore), Lehtimaki, T. (Terho), Lessel, D. (Davor), Ligthart, L. (Lannie), Litterman, N. (Nadia), van den Maagdenberg, A. (Arn), Macaya, A. (Alfons), Malik, R. (Rainer), Mangino, M. (Massimo), McMahon, G. (George), Muller-Myhsok, B. (Bertram), Neale, B. M. (Benjamin M.), Northover, C. (Carrie), Nyholt, D. R. (Dale R.), Palotie, A. (Aarno), Palta, P. (Priit), Pedersen, L. (Linda), Pedersen, N. (Nancy), Posthuma, D. (Danielle), Pozo-Rosich, P. (Patricia), Pressman, A. (Alice), Raitakari, O. (Olli), Schurks, M. (Markus), Sintas, C. (Celia), Steinberg, S. (Stacy), Strachan, D. (David), Terwindt, G. (Gisela), Vila-Pueyo, M. (Marta), Wessman, M. (Maija), Winsvold, B. S. (Bendik S.), Zhao, H. (Huiying), and Zwart, J.-A. (John-Anker)
Abstract: Objective: To assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response. Methods: We interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome. Results: A twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05–1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26–8.14]). No association was found for acute treatment with non–migraine-specific weak analgesics and prophylactic treatment response. Conclusions: The migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine.
Published: 2019

22. Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation

Author: Bis, J.C. (Joshua), Jian, X. (Xueqiu), Kunkle, B.W. (Brian W.), Chen, Y. (Yuning), Hamilton-Nelson, K.L. (Kara L.), Bush, W.S. (William S.), Salerno, W.J. (William J.), Lancour, D. (Daniel), Ma, Y. (Yiyi), Renton, A. (Alan), Marcora, E. (Edoardo), Farrell, J.J. (John J.), Zhao, Y. (Yi), Qu, L. (Liming), Ahmad, S. (Shahzad), Amin, N. (Najaf), Amouyel, P. (Philippe), Beecham, G.W., Below, J.E. (Jennifer E.), Campion, D. (Dominique), Charbonnier, C. (Camille), Chung, J. (Jaeyoon), Crane, L.M.A., Cruchaga, C. (Carlos), Cupples, L.A. (L. Adrienne), Dartigues, J.-F., Debette, S. (Stéphanie), Deleuze, J.-F. (Jean-François), Fulton, L. (Lucinda), Gabriel, S.B. (Stacey), Genin, E. (Emmanuelle), Gibbs, R.A. (Richard A.), Goate, A.M. (Alison), Grenier-Boley, B. (Benjamin), Gupta, N. (Namrata), Haines, J.L. (Jonathan), Havulinna, A.S. (Aki), Helisalmi, S. (Seppo), Hiltunen, M. (Mikko), Howrigan, D.P. (Daniel P.), Ikram, M.A. (Arfan), Kaprio, J. (Jaakko), Konrad, J. (Jan), Kuzma, A. (Amanda), Lander, E.S. (Eric), Lathrop, M. (Mark), Lehtimäki, T. (Terho), Lin, H. (Honghuang), Mattila, K. (Kari), Mayeux, R. (Richard), Muzny, D. (Donna), Nasser, W. (Waleed), Neale, B.M. (Benjamin), Nho, K. (Kwangsik), Nicolas, G. (Gaël), Patel, D. (Devanshi), Pericak-Vance, M.A. (Margaret), Perola, M. (Markus), Psaty, B.M. (Bruce M.), Quenez, O. (Olivier), Rajabli, F. (Farid), Redon, R. (Richard), Reitz, C. (Christiane), Remes, A. (Anne), Salomaa, V. (Veikko), Sarnowski, C., Schmidt, H. (Helena), Schmidt, M. (Michael), Schmidt, R. (Reinhold), Soininen, H. (H.), Thornton, T.A. (Timothy A.), Tosto, G. (G.), Tzourio, C. (Christophe), Lee, S.J. (Sven) van der, Duijn, C.M. (Cornelia) van, Vardarajan, B.N. (Badri), Wang, W. (Weixin), Wijsman, E.M. (Ellen), Wilson, R.K. (Richard K.), Witten, D. (Daniela), Worley, K.C. (Kim C.), Zhang, X. (Xiaoling), Bellenguez, C. (Céline), Lambert, J.-C. (J.), Kurki, M.I. (Mitja I.), Palotie, A. (Aarno), Daly, M. (Mark), Boerwinkle, E. (Eric), Lunetta, K.L. (Kathryn), DeStefano, A.L. (Anita), Dupuis, J. (Josée), Martin, E.R. (Eden R.), Schellenberg, G.D. (Gerard), Seshadri, S. (Sudha), Naj, A.C. (Adam C.), Fornage, M. (Myriam), Farrer, L.A. (Lindsay), Bis, J.C. (Joshua), Jian, X. (Xueqiu), Kunkle, B.W. (Brian W.), Chen, Y. (Yuning), Hamilton-Nelson, K.L. (Kara L.), Bush, W.S. (William S.), Salerno, W.J. (William J.), Lancour, D. (Daniel), Ma, Y. (Yiyi), Renton, A. (Alan), Marcora, E. (Edoardo), Farrell, J.J. (John J.), Zhao, Y. (Yi), Qu, L. (Liming), Ahmad, S. (Shahzad), Amin, N. (Najaf), Amouyel, P. (Philippe), Beecham, G.W., Below, J.E. (Jennifer E.), Campion, D. (Dominique), Charbonnier, C. (Camille), Chung, J. (Jaeyoon), Crane, L.M.A., Cruchaga, C. (Carlos), Cupples, L.A. (L. Adrienne), Dartigues, J.-F., Debette, S. (Stéphanie), Deleuze, J.-F. (Jean-François), Fulton, L. (Lucinda), Gabriel, S.B. (Stacey), Genin, E. (Emmanuelle), Gibbs, R.A. (Richard A.), Goate, A.M. (Alison), Grenier-Boley, B. (Benjamin), Gupta, N. (Namrata), Haines, J.L. (Jonathan), Havulinna, A.S. (Aki), Helisalmi, S. (Seppo), Hiltunen, M. (Mikko), Howrigan, D.P. (Daniel P.), Ikram, M.A. (Arfan), Kaprio, J. (Jaakko), Konrad, J. (Jan), Kuzma, A. (Amanda), Lander, E.S. (Eric), Lathrop, M. (Mark), Lehtimäki, T. (Terho), Lin, H. (Honghuang), Mattila, K. (Kari), Mayeux, R. (Richard), Muzny, D. (Donna), Nasser, W. (Waleed), Neale, B.M. (Benjamin), Nho, K. (Kwangsik), Nicolas, G. (Gaël), Patel, D. (Devanshi), Pericak-Vance, M.A. (Margaret), Perola, M. (Markus), Psaty, B.M. (Bruce M.), Quenez, O. (Olivier), Rajabli, F. (Farid), Redon, R. (Richard), Reitz, C. (Christiane), Remes, A. (Anne), Salomaa, V. (Veikko), Sarnowski, C., Schmidt, H. (Helena), Schmidt, M. (Michael), Schmidt, R. (Reinhold), Soininen, H. (H.), Thornton, T.A. (Timothy A.), Tosto, G. (G.), Tzourio, C. (Christophe), Lee, S.J. (Sven) van der, Duijn, C.M. (Cornelia) van, Vardarajan, B.N. (Badri), Wang, W. (Weixin), Wijsman, E.M. (Ellen), Wilson, R.K. (Richard K.), Witten, D. (Daniela), Worley, K.C. (Kim C.), Zhang, X. (Xiaoling), Bellenguez, C. (Céline), Lambert, J.-C. (J.), Kurki, M.I. (Mitja I.), Palotie, A. (Aarno), Daly, M. (Mark), Boerwinkle, E. (Eric), Lunetta, K.L. (Kathryn), DeStefano, A.L. (Anita), Dupuis, J. (Josée), Martin, E.R. (Eden R.), Schellenberg, G.D. (Gerard), Seshadri, S. (Sudha), Naj, A.C. (Adam C.), Fornage, M. (Myriam), and Farrer, L.A. (Lindsay)
Abstract: The Alzheimer’s Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 contro
Published: 2018
Full Text: View/download PDF

23. Erratum to: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author: Waage, J. (Johannes), Standl, M. (Marie), Curtin, J.A. (John), Jessen, L.E. (Leon E.), Thorsen, J. (Jonathan), Tian, C. (Chao), Schoettler, N. (Nathan), Flores, C. (Carlos), Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Anto, J.M. (Josep), Barreto-Luis, A. (Amalia), Baurecht, H. (Hansjörg), Beijsterveldt, C.E.M. (Toos) van, Bleecker, E.R. (E.), Bonàs-Guarch, S. (Silvia), Boomsma, D.I. (Dorret), Brix, S. (Susanne), Bunyavanich, S. (Supinda), Burchard, E.G. (Esteban), Chen, Z. (Zhanghua), Curjuric, I. (Ivan), Custovic, A. (Adnan), Dekker, H.T. (Herman) den, Dharmage, S.C. (Shyamali C.), Dmitrieva, J. (Julia), Duijts, L. (Liesbeth), Ege, M. (Markus), Gauderman, W.J. (W James), Georges, M. (Michel), Gieger, C. (Christian), Gilliland, D.G. (Gary), Granell, R. (Raquel), Gui, H. (Hongsheng), Hansen, T. (Torben), Heinrich, J. (Joachim), Henderson, J. (John), Hernandez-Pacheco, N. (Natalia), Holt, P.G. (Patrick), Imboden, M. (Medea), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Jarvis, D.L. (Deborah), Jensen, K.K. (Kamilla K.), Jonsdottir, I. (Ingileif), Kabesch, M. (Michael), Kaprio, J. (Jaakko), Kumar, A. (Ashish), Lee, Y.-A. (Young-Ae), Levin, A.M. (Albert M.), Li, X. (Xingnan), Lorenzo-Diaz, F. (Fabian), Melén, E. (Erik), Mercader, J.M. (Josep M.), Meyers, D.A. (Deborah A.), Myers, R.A. (Rachel A.), Nicolae, D. (Dan), Nohr, C. (Christian), Palviainen, T. (Teemu), Paternoster, L. (Lavinia), Pennell, C.E. (Craig E.), Pershagen, G. (Göran), Pino-Yanes, M. (Maria), Probst-Hensch, N.M. (Nicole M.), Rüschendorf, F. (Franz), Simpson, A. (Angela), Zwart, J-A. (John-Anker), Sunyer, J. (Jordi), Sveinbjornsson, G. (Gardar), Thiering, E. (Elisabeth), Thompson, P.J. (Philip J.), Torrent, M. (Maties), Torrents, D. (David), Tung, J.Y. (Joyce Y.), Wang, C.A. (Carol A.), Weidinger, S. (Stephan), Weiss, S.T. (Scott T.), Willemsen, G.A.H.M. (Gonneke), Williams, L.K. (L. Keoki), Ober, C. (Carole), Hinds, D.A. (David A.), Ferreira, M.A. (Manuel), Bisgaard, H. (Hans), Arnold, A.M. (Alice), Strachan, D.P. (David), Bønnelykke, K. (Klaus), Waage, J. (Johannes), Standl, M. (Marie), Curtin, J.A. (John), Jessen, L.E. (Leon E.), Thorsen, J. (Jonathan), Tian, C. (Chao), Schoettler, N. (Nathan), Flores, C. (Carlos), Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Anto, J.M. (Josep), Barreto-Luis, A. (Amalia), Baurecht, H. (Hansjörg), Beijsterveldt, C.E.M. (Toos) van, Bleecker, E.R. (E.), Bonàs-Guarch, S. (Silvia), Boomsma, D.I. (Dorret), Brix, S. (Susanne), Bunyavanich, S. (Supinda), Burchard, E.G. (Esteban), Chen, Z. (Zhanghua), Curjuric, I. (Ivan), Custovic, A. (Adnan), Dekker, H.T. (Herman) den, Dharmage, S.C. (Shyamali C.), Dmitrieva, J. (Julia), Duijts, L. (Liesbeth), Ege, M. (Markus), Gauderman, W.J. (W James), Georges, M. (Michel), Gieger, C. (Christian), Gilliland, D.G. (Gary), Granell, R. (Raquel), Gui, H. (Hongsheng), Hansen, T. (Torben), Heinrich, J. (Joachim), Henderson, J. (John), Hernandez-Pacheco, N. (Natalia), Holt, P.G. (Patrick), Imboden, M. (Medea), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Jarvis, D.L. (Deborah), Jensen, K.K. (Kamilla K.), Jonsdottir, I. (Ingileif), Kabesch, M. (Michael), Kaprio, J. (Jaakko), Kumar, A. (Ashish), Lee, Y.-A. (Young-Ae), Levin, A.M. (Albert M.), Li, X. (Xingnan), Lorenzo-Diaz, F. (Fabian), Melén, E. (Erik), Mercader, J.M. (Josep M.), Meyers, D.A. (Deborah A.), Myers, R.A. (Rachel A.), Nicolae, D. (Dan), Nohr, C. (Christian), Palviainen, T. (Teemu), Paternoster, L. (Lavinia), Pennell, C.E. (Craig E.), Pershagen, G. (Göran), Pino-Yanes, M. (Maria), Probst-Hensch, N.M. (Nicole M.), Rüschendorf, F. (Franz), Simpson, A. (Angela), Zwart, J-A. (John-Anker), Sunyer, J. (Jordi), Sveinbjornsson, G. (Gardar), Thiering, E. (Elisabeth), Thompson, P.J. (Philip J.), Torrent, M. (Maties), Torrents, D. (David), Tung, J.Y. (Joyce Y.), Wang, C.A. (Carol A.), Weidinger, S. (Stephan), Weiss, S.T. (Scott T.), Willemsen, G.A.H.M. (Gonneke), Williams, L.K. (L. Keoki), Ober, C. (Carole), Hinds, D.A. (David A.), Ferreira, M.A. (Manuel), Bisgaard, H. (Hans), Arnold, A.M. (Alice), Strachan, D.P. (David), and Bønnelykke, K. (Klaus)
Abstract: In the version of this article initially published, in Fig. 3, the _y_-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.
Published: 2018
Full Text: View/download PDF

24. Childhood aggression and the co-occurrence of behavioural and emotional problems

Author: Bartels, M. (Meike), Hendriks, A. (Anne), Mauri, M. (Matteo), Krapohl, E. (Eva), Whipp, A. (Alyce), Bolhuis, K. (Koen), Conde, L.C. (Lucia Colodro), Luningham, J. (Justin), Fung Ip, H. (Hill), Hagenbeek, F. (Fiona), Roetman, P. (Peter), Gatej, R. (Raluca), Lamers, A. (Audri), Nivard, M. (Michel), Dongen, J. (Jenny) van, Lu, Y. (Yi), Middeldorp, C.M. (Christel), Beijsterveldt, C.E.M. (Toos) van, Vermeiren, R.R.J.M. (Robert R.J.M.), Hankemeijer, T. (Thomas), Kluft, C. (Cees), Medland, S.E. (Sarah), Lundström, S. (Sebastian), Rose, R.J. (Richard), Pulkkinen, L. (Lea), Vuoksimaa, E. (Eero), Korhonen, T. (Tellervo), Martin, N.G. (Nicholas), Lubke, G.H. (Gitta), Finkenauer, C. (Catrin), Fanos, V. (Vassilios), Tiemeier, H.W. (Henning), Lichtenstein, P. (Paul), Plomin, R. (Robert), Kaprio, J. (Jaakko), Boomsma, D.I. (Dorret), Bartels, M. (Meike), Hendriks, A. (Anne), Mauri, M. (Matteo), Krapohl, E. (Eva), Whipp, A. (Alyce), Bolhuis, K. (Koen), Conde, L.C. (Lucia Colodro), Luningham, J. (Justin), Fung Ip, H. (Hill), Hagenbeek, F. (Fiona), Roetman, P. (Peter), Gatej, R. (Raluca), Lamers, A. (Audri), Nivard, M. (Michel), Dongen, J. (Jenny) van, Lu, Y. (Yi), Middeldorp, C.M. (Christel), Beijsterveldt, C.E.M. (Toos) van, Vermeiren, R.R.J.M. (Robert R.J.M.), Hankemeijer, T. (Thomas), Kluft, C. (Cees), Medland, S.E. (Sarah), Lundström, S. (Sebastian), Rose, R.J. (Richard), Pulkkinen, L. (Lea), Vuoksimaa, E. (Eero), Korhonen, T. (Tellervo), Martin, N.G. (Nicholas), Lubke, G.H. (Gitta), Finkenauer, C. (Catrin), Fanos, V. (Vassilios), Tiemeier, H.W. (Henning), Lichtenstein, P. (Paul), Plomin, R. (Robert), Kaprio, J. (Jaakko), and Boomsma, D.I. (Dorret)
Abstract: Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopa
Published: 2018
Full Text: View/download PDF

25. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), Deary, I.J. (Ian), Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), and Deary, I.J. (Ian)
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the c
Published: 2018
Full Text: View/download PDF

26. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author: Waage, J. (Johannes), Standl, M. (Marie), Curtin, J. A. (John A.), Jessen, L. E. (Leon E.), Thorsen, J. (Jonathan), Tian, C. (Chao), Schoettler, N. (Nathan), Flores, C. (Carlos), Abdellaoui, A. (Abdel), Ahluwalia, T. S. (Tarunveer S.), Alves, A. C. (Alexessander C.), Amaral, A. F. (Andre F. S.), Anto, J. M. (Josep M.), Arnold, A. (Andreas), Barreto-Luis, A. (Amalia), Baurecht, H. (Hansjoerg), van Beijsterveldt, C. E. (Catharina E. M.), Bleecker, E. R. (Eugene R.), Bonas-Guarch, S. (Silvia), Boomsman, D. I. (Dorret I.), Brix, S. (Susanne), Bunyavanich, S. (Supinda), Burchard, E. G. (Esteban G.), Chen, Z. (Zhanghua), Curjuric, I. (Ivan), Custovic, A. (Adnan), den Dekker, H. T. (Herman T.), Dharmage, S. C. (Shyamali C.), Dmitrieva, J. (Julia), Duijts, L. (Liesbeth), Ege, M. J. (Markus J.), Gauderman, W. J. (W. James), Georges, M. (Michel), Gieger, C. (Christian), Gilliland, F. (Frank), Granell, R. (Raquel), Gui, H. (Hongsheng), Hansen, T. (Torben), Heinrich, J. (Joachim), Henderson, J. (John), Hernandez-Pacheco, N. (Natalia), Holt, P. (Patrick), Imboden, M. (Medea), Jaddoe, V. W. (Vincent W. V.), Järvelin, M.-R. (Marjo-Riitta), Jarvis, D. L. (Deborah L.), Jensen, K. K. (Kamilla K.), Jonsdottir, I. (Ingileif), Kabesch, M. (Michael), Kaprio, J. (Jaakko), Kumar, A. (Ashish), Lee, Y.-A. (Young-Ae), Levin, A. M. (Albert M.), Li, X. (Xingnan), Lorenzo-Diaz, F. (Fabian), Melen, E. (Erik), Mercader, J. M. (Josep M.), Meyers, D. A. (Deborah A.), Myers, R. (Rachel), Nicolae, D. L. (Dan L.), Nohr, E. A. (Ellen A.), Palviainen, T. (Teemu), Paternoster, L. (Lavinia), Pennell, C. E. (Craig E.), Pershagen, G. (Goran), Pino-Yanes, M. (Maria), Probst-Hensch, N. M. (Nicole M.), Ruschendorf, F. (Franz), Simpson, A. (Angela), Stefansson, K. (Kari), Sunyer, J. (Jordi), Sveinbjornsson, G. (Gardar), Thiering, E. (Elisabeth), Thompson, P. J. (Philip J.), Torrent, M. (Maties), Torrents, D. (David), Tung, J. Y. (Joyce Y.), Wang, C. A. (Carol A.), Weidinger, S. (Stephan), Weiss, S. (Scott), Willemsen, G. (Gonneke), Williams, L. K. (L. Keoki), Ober, C. (Carole), Hinds, D. A. (David A.), Ferreira, M. A. (Manuel A.), Bisgaard, H. (Hans), Strachan, D. P. (David P.), Bonnelykke, K. (Klaus), Waage, J. (Johannes), Standl, M. (Marie), Curtin, J. A. (John A.), Jessen, L. E. (Leon E.), Thorsen, J. (Jonathan), Tian, C. (Chao), Schoettler, N. (Nathan), Flores, C. (Carlos), Abdellaoui, A. (Abdel), Ahluwalia, T. S. (Tarunveer S.), Alves, A. C. (Alexessander C.), Amaral, A. F. (Andre F. S.), Anto, J. M. (Josep M.), Arnold, A. (Andreas), Barreto-Luis, A. (Amalia), Baurecht, H. (Hansjoerg), van Beijsterveldt, C. E. (Catharina E. M.), Bleecker, E. R. (Eugene R.), Bonas-Guarch, S. (Silvia), Boomsman, D. I. (Dorret I.), Brix, S. (Susanne), Bunyavanich, S. (Supinda), Burchard, E. G. (Esteban G.), Chen, Z. (Zhanghua), Curjuric, I. (Ivan), Custovic, A. (Adnan), den Dekker, H. T. (Herman T.), Dharmage, S. C. (Shyamali C.), Dmitrieva, J. (Julia), Duijts, L. (Liesbeth), Ege, M. J. (Markus J.), Gauderman, W. J. (W. James), Georges, M. (Michel), Gieger, C. (Christian), Gilliland, F. (Frank), Granell, R. (Raquel), Gui, H. (Hongsheng), Hansen, T. (Torben), Heinrich, J. (Joachim), Henderson, J. (John), Hernandez-Pacheco, N. (Natalia), Holt, P. (Patrick), Imboden, M. (Medea), Jaddoe, V. W. (Vincent W. V.), Järvelin, M.-R. (Marjo-Riitta), Jarvis, D. L. (Deborah L.), Jensen, K. K. (Kamilla K.), Jonsdottir, I. (Ingileif), Kabesch, M. (Michael), Kaprio, J. (Jaakko), Kumar, A. (Ashish), Lee, Y.-A. (Young-Ae), Levin, A. M. (Albert M.), Li, X. (Xingnan), Lorenzo-Diaz, F. (Fabian), Melen, E. (Erik), Mercader, J. M. (Josep M.), Meyers, D. A. (Deborah A.), Myers, R. (Rachel), Nicolae, D. L. (Dan L.), Nohr, E. A. (Ellen A.), Palviainen, T. (Teemu), Paternoster, L. (Lavinia), Pennell, C. E. (Craig E.), Pershagen, G. (Goran), Pino-Yanes, M. (Maria), Probst-Hensch, N. M. (Nicole M.), Ruschendorf, F. (Franz), Simpson, A. (Angela), Stefansson, K. (Kari), Sunyer, J. (Jordi), Sveinbjornsson, G. (Gardar), Thiering, E. (Elisabeth), Thompson, P. J. (Philip J.), Torrent, M. (Maties), Torrents, D. (David), Tung, J. Y. (Joyce Y.), Wang, C. A. (Carol A.), Weidinger, S. (Stephan), Weiss, S. (Scott), Willemsen, G. (Gonneke), Williams, L. K. (L. Keoki), Ober, C. (Carole), Hinds, D. A. (David A.), Ferreira, M. A. (Manuel A.), Bisgaard, H. (Hans), Strachan, D. P. (David P.), and Bonnelykke, K. (Klaus)
Abstract: Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis. An Author Correction to this article was published on 16 August 2018. https://www.nature.com/articles/s41588-018-0197-6
Published: 2018

27. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

Author: Aschard, H. (Hugues), Tobin, M. D. (Martin D), Hancock, D. B. (Dana B), Skurnik, D. (David), Sood, A. (Akshay), James, A. (Alan), Smith, A. V. (Albert Vernon), Manichaikul, A. W. (Ani W), Campbell, A. (Archie), Prins, B. P. (Bram P), Hayward, C. (Caroline), Loth, D. W. (Daan W), Porteous, D. J. (David J), Strachan, D. P. (David P), Zeggini, E. (Eleftheria), O’Connor, G. T. (George T), Brusselle, G. G. (Guy G), Boezen, H. M. (H Marike), Schulz, H. (Holger), Deary, I. J. (Ian J), Hall, I. P. (Ian P), Rudan, I. (Igor), Kaprio, J. (Jaakko), Wilson, J. F. (James F), Wilk, J. B. (Jemma B), Huffman, J. E. (Jennifer E), Zhao, J. H. (Jing Hua), de Jong, K. (Kim), Lyytikäinen, L.-P. (Leo-Pekka), Wain, L. V. (Louise V), Järvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Fornage, M. (Myriam), Polasek, O. (Ozren), Cassano, P. A. (Patricia A), Barr, R. G. (R Graham), Rawal, R. (Rajesh), Harris, S. E. (Sarah E), Gharib, S. A. (Sina A), Enroth, S. (Stefan), Heckbert, S. R. (Susan R), Lehtimäki, T. (Terho), Gyllensten, U. (Ulf), Understanding Society Scientific Group, Jackson, V. E. (Victoria E), Gudnason, V. (Vilmundur), Tang, W. (Wenbo), Dupuis, J. (Josée), Artigas, M. S. (María Soler), Joshi, A. D. (Amit D), London, S. J. (Stephanie J), Kraft, P. (Peter), Groningen Research Institute for Asthma and COPD (GRIAC), and Life Course Epidemiology (LCE)
Subjects: RISK, Medicin och hälsovetenskap, Science & Technology, PREDICTION, 0104 Statistics, respiratory system, genetic risk score, Medical and Health Sciences, DISEASE, smoking, gene-environment interaction, respiratory tract diseases, LUNG-FUNCTION, OPPORTUNITIES, 1117 Public Health And Health Services, FEV1/FVC, EPIDEMIOLOGY, OBSTRUCTION, GENOME-WIDE ASSOCIATION, ENVIRONMENT INTERACTIONS, gene–environment interaction, Life Sciences & Biomedicine, Public, Environmental & Occupational Health
Abstract: Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (βint = −0.036, 95% confidence interval, −0.040 to −0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
Published: 2017

28. Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy

Author: Kangas, R. (Reeta), Törmäkangas, T. (Timo), Fey, V. (Vidal), Pursiheimo, J. (Juha), Miinalainen, I. (Ilkka), Alen, M. (Markku), Kaprio, J. (Jaakko), Sipilä, S. (Sarianna), Säämänen, A.-M. (Anna-Marja), Kovanen, V. (Vuokko), Laakkonen, E. K. (Eija K.), Kangas, R. (Reeta), Törmäkangas, T. (Timo), Fey, V. (Vidal), Pursiheimo, J. (Juha), Miinalainen, I. (Ilkka), Alen, M. (Markku), Kaprio, J. (Jaakko), Sipilä, S. (Sarianna), Säämänen, A.-M. (Anna-Marja), Kovanen, V. (Vuokko), and Laakkonen, E. K. (Eija K.)
Abstract: Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein- and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age +HRT -related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17β-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17β-estradiol, fat-, glucose- and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature.
Published: 2017

29. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author: Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)
Abstract: The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa
Published: 2017
Full Text: View/download PDF

30. Rare and low-frequency coding variants alter human adult height

Author: Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), Lettre, G. (Guillaume), Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), and Lettre, G. (Guillaume)
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of I
Published: 2017
Full Text: View/download PDF

31. An epigenome-wide association study meta-analysis of educational attainment

Author: Karlsson Linnér, R. (R.), Marioni, R.E. (Riccardo), Rietveld, C.A. (Niels), Simpkin, A.J. (A. J.), Davies, N.M. (N. M.), Watanabe, K. (K.), Armstrong, N.J. (Nicola J.), Auro, K. (Kirsi), Baumbach, C. (Clemens), Bonder, M.J. (Marc), Buchwald, J. (J.), Fiorito, G. (G.), Ismail, K. (K.), Iurato, S. (S.), Joensuu, A. (Anni), Karell, P. (P.), Kasela, S. (Silva), Lahti, J. (Jari), McRae, A.F. (A. F.), Mandaviya, P.R. (Pooja), Seppälä, I. (Ilkka), Wang, Y. (Y.), Baglietto, L. (L.), Binder, E.B. (Elisabeth), Harris, S.E. (Sarah), Hodge, A.M. (A. M.), Horvath, S. (S.), Hurme, M. (M.), Johannesson, M. (Magnus), Latvala, A. (Antti), Mather, R., Medland, S.E. (Sarah), Metspalu, A. (A.), Milani, L. (Lili), Milne, R.L. (R. L.), Pattie, A. (Alison), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polidoro, S. (Silvia), Räikkönen, K. (Katri), Severi, G. (Gianluca), Starr, J.M. (John), Stolk, L. (Lisette), Waldenberger, M. (M.), Hagen, K. (Knut), Esko, T. (Tõnu), Franke, L. (Lude), Gieger, C. (Christian), Giles, G.G. (G. G.), Hägg, S. (Sara), Jousilahti, P. (Pekka), Kaprio, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Martin, N.G. (N. G.), Meurs, J. (J.) van, Ollikainen, M. (M.), Perola, M. (M.), Posthuma, D. (Danielle), Raitakari, O.T. (O. T.), Sachdev, P.S. (Perminder), Taskesen, E. (Erdogan), Uitterlinden, A.G. (André), Vineis, P. (Paolo), Wijmenga, C. (Ciska), Wright, M.J. (M. J.), Relton, C.L. (Caroline), Davey Smith, G. (G.), Deary, I.J. (Ian), Koellinger, P.D. (P. D.), Benjamin, D.J. (D. J.), Karlsson Linnér, R. (R.), Marioni, R.E. (Riccardo), Rietveld, C.A. (Niels), Simpkin, A.J. (A. J.), Davies, N.M. (N. M.), Watanabe, K. (K.), Armstrong, N.J. (Nicola J.), Auro, K. (Kirsi), Baumbach, C. (Clemens), Bonder, M.J. (Marc), Buchwald, J. (J.), Fiorito, G. (G.), Ismail, K. (K.), Iurato, S. (S.), Joensuu, A. (Anni), Karell, P. (P.), Kasela, S. (Silva), Lahti, J. (Jari), McRae, A.F. (A. F.), Mandaviya, P.R. (Pooja), Seppälä, I. (Ilkka), Wang, Y. (Y.), Baglietto, L. (L.), Binder, E.B. (Elisabeth), Harris, S.E. (Sarah), Hodge, A.M. (A. M.), Horvath, S. (S.), Hurme, M. (M.), Johannesson, M. (Magnus), Latvala, A. (Antti), Mather, R., Medland, S.E. (Sarah), Metspalu, A. (A.), Milani, L. (Lili), Milne, R.L. (R. L.), Pattie, A. (Alison), Pedersen, N.L. (Nancy), Peters, A. (Annette), Polidoro, S. (Silvia), Räikkönen, K. (Katri), Severi, G. (Gianluca), Starr, J.M. (John), Stolk, L. (Lisette), Waldenberger, M. (M.), Hagen, K. (Knut), Esko, T. (Tõnu), Franke, L. (Lude), Gieger, C. (Christian), Giles, G.G. (G. G.), Hägg, S. (Sara), Jousilahti, P. (Pekka), Kaprio, J. (Jaakko), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Martin, N.G. (N. G.), Meurs, J. (J.) van, Ollikainen, M. (M.), Perola, M. (M.), Posthuma, D. (Danielle), Raitakari, O.T. (O. T.), Sachdev, P.S. (Perminder), Taskesen, E. (Erdogan), Uitterlinden, A.G. (André), Vineis, P. (Paolo), Wijmenga, C. (Ciska), Wright, M.J. (M. J.), Relton, C.L. (Caroline), Davey Smith, G. (G.), Deary, I.J. (Ian), Koellinger, P.D. (P. D.), and Benjamin, D.J. (D. J.)
Abstract: The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications - in our case, CpG methylation - and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.
Published: 2017
Full Text: View/download PDF

32. Genome-wide association study identifies 74 loci associated with educational attainment

Author: Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), Benjamin, D.J. (Daniel J.), Okbay, A. (Aysu), Beauchamp, J.P. (Jonathan), Fontana, M.A. (Mark Alan), Lee, J.J. (James J.), Pers, T.H. (Tune), Rietveld, C.A. (Cornelius A.), Turley, P. (Patrick), Chen, G.-B. (Guo-Bo), Emilsson, V. (Valur), Meddens, S.F.W. (S. Fleur W.), Oskarsson, S. (Sven), Pickrell, J.K. (Joseph K.), Thom, K. (Kevin), Timshel, P. (Pascal), Vlaming, R. (Ronald) de, Abdellaoui, A. (Abdel), Ahluwalia, T.S. (Tarunveer Singh), Bacelis, J. (Jonas), Baumbach, C. (Clemens), Bjornsdottir, G. (Gyda), Brandsma, J.H. (Johan), Pina Concas, M. (Maria), Derringer, J., Furlotte, N.A. (Nicholas A.), Galesloot, T.E. (Tessel), Girotto, S., Gupta, R. (Richa), Hall, L.M. (Leanne M.), Harris, S.E. (Sarah), Hofer, E., Horikoshi, M. (Momoko), Huffman, J.E. (Jennifer E.), Kaasik, K. (Kadri), Kalafati, I.-P. (Ioanna-Panagiota), Karlsson, R. (Robert), Kong, A. (Augustine), Lahti, J. (Jari), Lee, S.J. (Sven) van der, Deleeuw, C. (Christiaan), Lind, P.A. (Penelope), Lindgren, K.-O. (Karl-Oskar), Liu, T. (Tian), Mangino, M. (Massimo), Marten, J. (Jonathan), Mihailov, E. (Evelin), Miller, M. (Mike), Most, P.J. (Peter) van der, Oldmeadow, C. (Christopher), Payton, A. (Antony), Pervjakova, N. (Natalia), Peyrot, W.J. (Wouter ), Qian, Y. (Yong), Raitakari, O. (Olli), Rueedi, R. (Rico), Salvi, E. (Erika), Schmidt, B. (Börge), Schraut, K.E. (Katharina E.), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Poot, R.A. (Raymond), St Pourcain, B. (Beate), Teumer, A. (Alexander), Thorleifsson, G. (Gudmar), Verweij, N. (Niek), Vuckovic, D. (Dragana), Wellmann, J. (Juergen), Westra, H.J. (Harm-Jan), Yang, J. (Jingyun), Zhao, W. (Wei), Zhu, Z. (Zhihong), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Bakshi, A. (Andrew), Baumeister, S.E. (Sebastian), Biino, G. (Ginevra), Bønnelykke, K. (Klaus), Boyle, P.A. (Patricia), Campbell, H. (Harry), Cappuccio, F.P. (Francesco P.), Davies, G. (Gail), Neve, J.E. (Jan-Emmanuel) de, Deloukas, P. (Panagiotis), Demuth, I. (Ilja), Ding, J. (Jun), Eibich, P. (Peter), Eisele, L. (Lewin), Eklund, N. (Niina), Evans, D.M. (David), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Forstner, A.J. (Andreas), Gandin, I. (Ilaria), Gunnarsson, B. (Bjarni), Halldorsson, B.V. (Bjarni), Harris, T.B. (Tamara), Holliday, E.G. (Elizabeth), Heath, A.C. (Andrew C.), Hocking, L.J., Homuth, G. (Georg), Horan, M. (Mike), Hottenga, J.J. (Jouke Jan), Jager, P.L. (Philip) de, Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kähönen, M. (Mika), Kanoni, S. (Stavroula), Keltigangas-Järvinen, L. (Liisa), Kiemeney, L.A.L.M. (Bart), Kolcic, I. (Ivana), Koskinen, S. (Seppo), Kraja, A. (Aldi), Kroh, M. (Martin), Kutalik, Z. (Zoltán), Latvala, A. (Antti), Launer, L.J. (Lenore), Lebreton, M.P. (Maël P.), Levinson, D.F. (Douglas F.), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Loukola, A. (Anu), Madden, P.A. (Pamela), Mägi, R. (Reedik), Mäki-Opas, T. (Tomi), Marioni, R.E. (Riccardo), Marques-Vidal, P. (Pedro), Meddens, G.A. (Gerardus A.), Mcmahon, G. (George), Meisinger, C. (Christa), Meitinger, T. (Thomas), Milaneschi, Y. (Yusplitri), Milani, L. (Lili), Montgomery, G.W. (Grant), Myhre, R. (Ronny), Nelson, C.P. (Christopher P.), Nyholt, D.R. (Dale), Ollier, W.E.R. (William), Palotie, A. (Aarno), Paternoster, L. (Lavinia), Pedersen, N.L. (Nancy), Petrovic, K. (Katja), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Ring, S.M. (Susan M.), Robino, A. (Antonietta), Rostapshova, O. (Olga), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sanders, A.R. (Alan R.), Sarin, A.-P., Schmidt, R. (Reinhold), Scott, R.J. (Rodney), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Staessen, J.A. (Jan), Steinhagen-Thiessen, E. (Elisabeth), Strauch, K. (Konstantin), Terracciano, A., Tobin, M.D. (Martin), Ulivi, S. (Shelia), Vaccargiu, S. (Simona), Quaye, L. (Lydia), Rooij, F.J.A. (Frank) van, Venturini, C. (Cristina), Vinkhuyzen, A.A.E. (Anna A.), Völker, U. (Uwe), Völzke, H. (Henry), Vonk, J.M. (Judith), Vozzi, D. (Diego), Waage, J. (Johannes), Ware, E.B. (Erin B.), Willemsen, G.A.H.M. (Gonneke), Attia, J. (John), Bennett, D.A. (David A.), Berger, K. (Klaus), Bertram, L. (Lars), Bisgaard, H. (Hans), Boomsma, D.I. (Dorret), Borecki, I.B. (Ingrid), Bültmann, U. (Ute), Chabris, C.F. (Christopher F.), Cucca, F. (Francesco), Cusi, D. (Daniele), Deary, I.J. (Ian), Dedoussis, G.V. (George), Duijn, C.M. (Cornelia) van, Hagen, K. (Knut), Franke, B. (Barbara), Franke, L. (Lude), Gasparini, P. (Paolo), Gejman, P.V. (Pablo), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Gratten, J. (Jacob), Groenen, P.J.F. (Patrick), Gudnason, V. (Vilmundur), Harst, P. (Pim) van der, Hayward, C. (Caroline), Hinds, D.A. (David A.), Hoffmann, W. (Wolfgang), Hypponen, E. (Elina), Iacono, W.G. (William), Jacobsson, B. (Bo), Jarvelin, M.-R. (Marjo-Riitta), JöCkel, K.-H. (Karl-Heinz), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Lehtimäki, T. (Terho), Lehrer, S.F. (Steven F.), Magnusson, P.K. (Patrik), Martin, N.G. (Nicholas), McGue, M. (Matt), Metspalu, A. (Andres), Pendleton, N. (Neil), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pirastu, N. (Nicola), Pirastu, M. (Mario), Polasek, O. (Ozren), Posthuma, D. (Danielle), Power, C. (Christopher), Province, M.A. (Mike), Samani, N.J. (Nilesh), Schlessinger, D. (David), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas J.), Tiemeier, H.W. (Henning), Tung, J.Y. (Joyce Y.), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Vollenweider, P. (Peter), Weir, D.R. (David), Wilson, J.F. (James F.), Wright, A.F. (Alan), Conley, D.C. (Dalton C.), Krueger, R.F., Smith, A.V. (Davey), Hofman, A. (Albert), Laibson, D. (David), Medland, S.E. (Sarah), Meyer, M.N. (Michelle N.), Yang, J. (Joanna), Johannesson, M. (Magnus), Visscher, P.M. (Peter), Esko, T. (Tõnu), Koellinger, Ph.D. (Philipp), Cesarini, D. (David), and Benjamin, D.J. (Daniel J.)
Abstract: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Published: 2016
Full Text: View/download PDF

33. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author: Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), and Palotie, A. (Aarno)
Abstract: Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10-8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Published: 2016
Full Text: View/download PDF

34. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author: Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Published: 2016
Full Text: View/download PDF

35. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author: Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)
Abstract: Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
Published: 2016
Full Text: View/download PDF

36. Association of Forced Vital Capacity with the Developmental Gene NCOR2

Author: Minelli, C. (Cosetta), Dean, C.H. (Charlotte H.), Hind, M. (Matthew), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Siroux, V. (V.), Huikari, V. (Ville), Artigas, M.S., Evans, D.M. (David M.), Loth, D.W. (Daan), Bossé, Y. (Yohan), Postma, D.S. (Dirkje), Sin, D.D., Thompson, J.R. (John), Demenais, F. (Florence), Henderson, J. (John), Bouzigon, E. (Emmanuelle), Jarvis, D.L. (Deborah), Jarvelin, M.-R. (Marjo-Riitta), Burney, P.G., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Albert), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David P.), James, A.L. (Alan L.), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nicholas J.), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna M.), Jong, K. (Kim) de, Thyagarajan, B. (Bharat), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari E.), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan F.), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), MVonk, J. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome I.), Gao, W. (Wei), White, W.B. (Wendy), Rich, S.S. (Stephen S.), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D.J. (David), Smith, L.J. (Lewis J.), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.B. (A Bill), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah L.), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), Connor, G.T. (George) O', Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan C.), MStarr, J. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher J.), MBurkart, K. (Kristin), Beilby, J. (John), Kritchevsky, S.B. (Stephen B.), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O. (O'Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Wjst, M. (Matthias), Kim, W.J. (Woo Jin), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne B.), Wilson, J.F. (James F), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), MVerhamme, F. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), London, S.J. (Stephanie J), Minelli, C. (Cosetta), Dean, C.H. (Charlotte H.), Hind, M. (Matthew), Alves, A.C. (Alexessander Couto), Amaral, A.F.S. (André), Siroux, V. (V.), Huikari, V. (Ville), Artigas, M.S., Evans, D.M. (David M.), Loth, D.W. (Daan), Bossé, Y. (Yohan), Postma, D.S. (Dirkje), Sin, D.D., Thompson, J.R. (John), Demenais, F. (Florence), Henderson, J. (John), Bouzigon, E. (Emmanuelle), Jarvis, D.L. (Deborah), Jarvelin, M.-R. (Marjo-Riitta), Burney, P.G., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Albert), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David P.), James, A.L. (Alan L.), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nicholas J.), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna M.), Jong, K. (Kim) de, Thyagarajan, B. (Bharat), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari E.), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan F.), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), MVonk, J. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome I.), Gao, W. (Wei), White, W.B. (Wendy), Rich, S.S. (Stephen S.), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D.J. (David), Smith, L.J. (Lewis J.), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.B. (A Bill), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah L.), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), Connor, G.T. (George) O', Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan C.), MStarr, J. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher J.), MBurkart, K. (Kristin), Beilby, J. (John), Kritchevsky, S.B. (Stephen B.), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O. (O'Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Wjst, M. (Matthias), Kim, W.J. (Woo Jin), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne B.), Wilson, J.F. (James F), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), MVerhamme, F. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), and London, S.J. (Stephanie J)
Abstract: Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chil
Published: 2016
Full Text: View/download PDF

37. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author: Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Published: 2016
Full Text: View/download PDF

38. Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology

Author: Eising, E., Huisman, S.M.H. (Sjoerd M. H.), Mahfouz, A. (Ahmed), Vijfhuizen, L.S. (Lisanne S.), Stefansson, K. (Kari), Winsvold, B.S. (Bendik), Kurth, T. (Tobias), Ikram, M.A. (Arfan), Müller-Myhsok, B. (Bertram), Kaprio, J. (Jaakko), Boomsma, D.I. (Dorret), Duijn, C.M. (Cornelia) van, Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Quaye, L. (Lydia), Strachan, D.P. (David P.), Dermitzakis, E.T. (Emmanouil), Kubisch, C. (Christian), Smith, A.V. (Davey), Palotie, A. (Aarno), Chasman, D.I. (Daniel), Ferrari, M.D. (Michel), Terwindt, G.M. (Gisela), Stam, A.H. (Anine), Dimas, A.S. (Antigone), Lelieveldt, B.P.F. (Boudewijn), Maagdenberg, A.M.J.M. (Arn), Reinders, M.J. (Marcel), Eising, E., Huisman, S.M.H. (Sjoerd M. H.), Mahfouz, A. (Ahmed), Vijfhuizen, L.S. (Lisanne S.), Stefansson, K. (Kari), Winsvold, B.S. (Bendik), Kurth, T. (Tobias), Ikram, M.A. (Arfan), Müller-Myhsok, B. (Bertram), Kaprio, J. (Jaakko), Boomsma, D.I. (Dorret), Duijn, C.M. (Cornelia) van, Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Quaye, L. (Lydia), Strachan, D.P. (David P.), Dermitzakis, E.T. (Emmanouil), Kubisch, C. (Christian), Smith, A.V. (Davey), Palotie, A. (Aarno), Chasman, D.I. (Daniel), Ferrari, M.D. (Michel), Terwindt, G.M. (Gisela), Stam, A.H. (Anine), Dimas, A.S. (Antigone), Lelieveldt, B.P.F. (Boudewijn), Maagdenberg, A.M.J.M. (Arn), and Reinders, M.J. (Marcel)
Abstract: Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.
Published: 2016
Full Text: View/download PDF

39. Metabolic signatures of birthweight in 18 288 adolescents and adults

Author: Würtz, P. (Peter), Wang, Q. (Qin), Niironen, M. (Marjo), Tynkkynen, T. (Tuulia), Tiainen, M. (Mika), Drenos, F. (Fotios), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), Skilton, M. R. (Michael R.), Heikkilä, K. (Kauko), Pouta, A. (Anneli), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Rose, R. J. (Richard J.), Kajantie, E. (Eero), Perola, M. (Markus), Kaprio, J. (Jaakko), Eriksson, J. G. (Johan G.), Raitakari, O. T. (Olli T.), Lawlor, D. A. (Debbie A.), Smith, G. D. (George Davey), Järvelin, M.-R. (Marjo-Riitta), Ala-Korpela, M. (Mika), Auro, K. (Kirsi), Würtz, P. (Peter), Wang, Q. (Qin), Niironen, M. (Marjo), Tynkkynen, T. (Tuulia), Tiainen, M. (Mika), Drenos, F. (Fotios), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), Skilton, M. R. (Michael R.), Heikkilä, K. (Kauko), Pouta, A. (Anneli), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Rose, R. J. (Richard J.), Kajantie, E. (Eero), Perola, M. (Markus), Kaprio, J. (Jaakko), Eriksson, J. G. (Johan G.), Raitakari, O. T. (Olli T.), Lawlor, D. A. (Debbie A.), Smith, G. D. (George Davey), Järvelin, M.-R. (Marjo-Riitta), Ala-Korpela, M. (Mika), and Auro, K. (Kirsi)
Abstract: Background: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI). Results: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. Conclusions: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity
Published: 2016

40. Molecular mechanisms underlying variations in lung function: A systems genetics analysis

Author: Obeidat, M. (Ma'en), Hao, K. (Ke), Bossé, Y. (Yohan), Nickle, D.C. (David), Nie, Y. (Yunlong), Postma, D.S. (Dirkje), Laviolette, M. (Michel), Sandford, A. (Andrew), Daley, D. (Denise), Hogg, J.C. (James), Elliott, W.M., Fishbane, N. (Nick), Timens, W. (Wim), Hysi, P.G. (Pirro), Kaprio, J. (Jaakko), Wilson, J.F. (James F), Hui, J. (Jennie), Rawal, R. (Rajesh), Schulz, H. (Holger), Stubbe, B. (Beate), Hayward, C. (Caroline), Polasek, O. (Ozren), Jarvelin, M.-R. (Marjo-Riitta), Zhao, J.H. (Jing Hua), Jarvis, D.L. (Deborah L.), Kähönen, M. (Mika), Franceschini, N. (Nora), North, K.E. (Kari), Loth, D.W. (Daan), Brusselle, G.G. (Guy), Smith, A.V. (Davey), Gudnason, V. (Vilmundur), Bartz, T.M. (Traci M.), Wilk, J.B. (Jemma), O'Connor, G.T. (George), Cassano, P.A. (Patricia), Tang, W. (Wenbo), Wain, L.V. (Louise), Artigas, M.S., Gharib, S.A. (Sina), Strachan, D.P. (David P.), Sin, D.D., Tobin, M.D. (Martin), London, S.J. (Stephanie J.), Hall, I.P. (Ian), Paré, P.D. (Peter), Obeidat, M. (Ma'en), Hao, K. (Ke), Bossé, Y. (Yohan), Nickle, D.C. (David), Nie, Y. (Yunlong), Postma, D.S. (Dirkje), Laviolette, M. (Michel), Sandford, A. (Andrew), Daley, D. (Denise), Hogg, J.C. (James), Elliott, W.M., Fishbane, N. (Nick), Timens, W. (Wim), Hysi, P.G. (Pirro), Kaprio, J. (Jaakko), Wilson, J.F. (James F), Hui, J. (Jennie), Rawal, R. (Rajesh), Schulz, H. (Holger), Stubbe, B. (Beate), Hayward, C. (Caroline), Polasek, O. (Ozren), Jarvelin, M.-R. (Marjo-Riitta), Zhao, J.H. (Jing Hua), Jarvis, D.L. (Deborah L.), Kähönen, M. (Mika), Franceschini, N. (Nora), North, K.E. (Kari), Loth, D.W. (Daan), Brusselle, G.G. (Guy), Smith, A.V. (Davey), Gudnason, V. (Vilmundur), Bartz, T.M. (Traci M.), Wilk, J.B. (Jemma), O'Connor, G.T. (George), Cassano, P.A. (Patricia), Tang, W. (Wenbo), Wain, L.V. (Louise), Artigas, M.S., Gharib, S.A. (Sina), Strachan, D.P. (David P.), Sin, D.D., Tobin, M.D. (Martin), London, S.J. (Stephanie J.), Hall, I.P. (Ian), and Paré, P.D. (Peter)
Abstract: Background: Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in
Published: 2015
Full Text: View/download PDF

41. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), Mohlke, K.L. (Karen), Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), and Mohlke, K.L. (Karen)
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10-8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015
Full Text: View/download PDF

42. The impact of low-frequency and rare variants on lipid levels

Author: Surakka, I. (Ida), Horikoshi, M. (Momoko), Mägi, R. (Reedik), Sarin, A.-P., Mahajan, A. (Anubha), Lagou, V. (Vasiliki), Marullo, L. (Letizia), Ferreira, T. (Teresa), Miraglio, B. (Benjamin), Timonen, S. (Sanna), Kettunen, J. (Johannes), Pirinen, M. (Matti), Karjalainen, J. (Juha), Thorleifsson, G. (Gudmar), Hägg, S. (Sara), Hottenga, J.J. (Jouke Jan), Isaacs, A.J. (Aaron), Ladenvall, C. (Claes), Beekman, M. (Marian), Esko, T. (Tõnu), Ried, J.S. (Janina), Nelson, C.P. (Christopher P.), Willenborg, C. (Christina), Gustafsson, S. (Stefan), Westra, H.J. (Harm-Jan), Blades, M. (Matthew), De Craen, A.J.M. (Anton J. M.), Geus, E.J.C. (Eco) de, Deelen, J. (Joris), Grallert, H. (Harald), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hengstenberg, C. (Christian), Houwing-Duistermaat, J.J. (Jeanine), Hypponen, E. (Elina), Karssen, L.C. (Lennart), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Magnusson, P.K. (Patrik), Mihailov, E. (Evelin), Müller-Nurasyid, M. (Martina), Mpindi, J.-P. (John-Patrick), Pedersen, N.L. (Nancy L.), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pers, T.H. (Tune), Peters, A. (Annette), Rung, J. (Johan), Smit, J.H. (Johannes), Steinthorsdottir, V. (Valgerdur), Tobin, M.D. (Martin), Tsernikova, N. (Natalia), Leeuwen, E.M. (Elisa) van, Viikari, J. (Jorma), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), Kaprio, J. (Jaakko), Lind, L. (Lars), Gieger, C. (Christian), Metspalu, A. (Andres), Slagboom, P.E. (Eline), Groop, L. (Leif), Duijn, C.M. (Cornelia) van, Eriksson, J.G. (Johan G.), Jula, A. (Antti), Salomaa, V. (Veikko), Boomsma, D.I. (Dorret), Power, C. (Christopher), Raitakari, O.T. (Olli T.), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Thorsteinsdottir, U. (Unnur), Franke, L. (Lude), Ikonen, E. (Elina), Kallioniemi, O. (Olli), Pietiäinen, V. (Vilja), Lindgren, C.M. (Cecilia M.), Zwart, J-A. (John-Anker), Palotie, A. (Aarno), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Prokopenko, I. (Inga), Ripatti, S. (Samuli), Surakka, I. (Ida), Horikoshi, M. (Momoko), Mägi, R. (Reedik), Sarin, A.-P., Mahajan, A. (Anubha), Lagou, V. (Vasiliki), Marullo, L. (Letizia), Ferreira, T. (Teresa), Miraglio, B. (Benjamin), Timonen, S. (Sanna), Kettunen, J. (Johannes), Pirinen, M. (Matti), Karjalainen, J. (Juha), Thorleifsson, G. (Gudmar), Hägg, S. (Sara), Hottenga, J.J. (Jouke Jan), Isaacs, A.J. (Aaron), Ladenvall, C. (Claes), Beekman, M. (Marian), Esko, T. (Tõnu), Ried, J.S. (Janina), Nelson, C.P. (Christopher P.), Willenborg, C. (Christina), Gustafsson, S. (Stefan), Westra, H.J. (Harm-Jan), Blades, M. (Matthew), De Craen, A.J.M. (Anton J. M.), Geus, E.J.C. (Eco) de, Deelen, J. (Joris), Grallert, H. (Harald), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hengstenberg, C. (Christian), Houwing-Duistermaat, J.J. (Jeanine), Hypponen, E. (Elina), Karssen, L.C. (Lennart), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Magnusson, P.K. (Patrik), Mihailov, E. (Evelin), Müller-Nurasyid, M. (Martina), Mpindi, J.-P. (John-Patrick), Pedersen, N.L. (Nancy L.), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Pers, T.H. (Tune), Peters, A. (Annette), Rung, J. (Johan), Smit, J.H. (Johannes), Steinthorsdottir, V. (Valgerdur), Tobin, M.D. (Martin), Tsernikova, N. (Natalia), Leeuwen, E.M. (Elisa) van, Viikari, J. (Jorma), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), Kaprio, J. (Jaakko), Lind, L. (Lars), Gieger, C. (Christian), Metspalu, A. (Andres), Slagboom, P.E. (Eline), Groop, L. (Leif), Duijn, C.M. (Cornelia) van, Eriksson, J.G. (Johan G.), Jula, A. (Antti), Salomaa, V. (Veikko), Boomsma, D.I. (Dorret), Power, C. (Christopher), Raitakari, O.T. (Olli T.), Ingelsson, E. (Erik), Jarvelin, M.-R. (Marjo-Riitta), Thorsteinsdottir, U. (Unnur), Franke, L. (Lude), Ikonen, E. (Elina), Kallioniemi, O. (Olli), Pietiäinen, V. (Vilja), Lindgren, C.M. (Cecilia M.), Zwart, J-A. (John-Anker), Palotie, A. (Aarno), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Prokopenko, I. (Inga), and Ripatti, S. (Samuli)
Abstract: Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
Published: 2015
Full Text: View/download PDF

43. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

Author: Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P <.05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identi
Published: 2015
Full Text: View/download PDF

44. Age- and sex-specific causal effects of adiposity on cardiovascular risk factors

Author: Fall, M. (Magnus), Hägg, S. (Sara), Ploner, A. (Alexander), Mägi, R. (Reedik), Fischer, K. (Krista), Draisma, G. (Gerrit), Sarin, A.-P., Benyamin, B. (Beben), Ladenvall, C. (Claes), Åkerlund, M. (Mikael), Kals, M. (Mart), Esko, T. (Tõnu), Nelson, C.P. (Christopher P.), Kaakinen, M. (Marika), Huikari, V. (Ville), Mangino, M. (Massimo), Meirhaeghe, A. (Aline), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Kobl, M. (Michael), Grallert, H. (Harald), Dehghan, A. (Abbas), Kuningas, M. (Maris), Vries, P.S. (Paul) de, Bruijn, R.F.A.G. (Renée) de, Willems, S.M. (Sara), Heikkilä, K. (Kauko), Silventoinen, K. (Karri), Pietilainen, K.H. (Kirsi Hannele), Legry, V. (Vanessa), Giedraitis, V. (Vilmantas), Goumidi, L. (Louisa), Syvanen, A.C., Strauch, K. (Konstantin), Koenig, W. (Wolfgang), Lichtner, P. (Peter), Herder, C. (Christian), Palotie, A. (Aarno), Menni, C. (Cristina), Uitterlinden, A.G. (André), Kuulasmaa, K. (Kari), Havulinna, A.S. (Aki), Moreno, L. (Luis), Gonzalez-Gross, M. (Marcela), Evans, A. (Alun), Tregouet, D.-A. (David-Alexandre), Yarnell, J.W.G. (John W.), Virtamo, J. (Jarmo), Ferrieres, J. (Jean), Veronesi, G. (Giovanni), Perola, M. (Markus), Arveiler, D. (Dominique), Brambilla, P. (Paolo), Lind, L. (Lars), Kaprio, J. (Jaakko), Hofman, A. (Albert), Stricker, B.H.Ch. (Bruno), Duijn, C.M. (Cornelia) van, Ikram, M.A. (Arfan), Franco, O.H. (Oscar), Cottel, D. (Dominique), Dallongeville, J., Hall, A.S. (Alistair), Jula, A. (Antti), Tobin, M.D. (Martin), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Gieger, C. (Christian), Samani, N.J. (Nilesh), Montgomery, G.W. (Grant), Whitfield, J. (John), Martin, N.G. (Nicholas), Groop, L. (Leif), Spector, T.D. (Timothy), Magnusson, P.K. (Patrik), Amouyel, P. (Philippe), Boomsma, D.I. (Dorret), Nilsson, P. (Peter), Jarvelin, M.-R. (Marjo-Riitta), Lyssenko, V. (Valeriya), Metspalu, A. (Andres), Strachan, D.P. (David), Salomaa, V. (Veikko), Ripatti, S. (Samuli), Pedersen, N.L. (Nancy), Prokopenko, I. (Inga), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Fall, M. (Magnus), Hägg, S. (Sara), Ploner, A. (Alexander), Mägi, R. (Reedik), Fischer, K. (Krista), Draisma, G. (Gerrit), Sarin, A.-P., Benyamin, B. (Beben), Ladenvall, C. (Claes), Åkerlund, M. (Mikael), Kals, M. (Mart), Esko, T. (Tõnu), Nelson, C.P. (Christopher P.), Kaakinen, M. (Marika), Huikari, V. (Ville), Mangino, M. (Massimo), Meirhaeghe, A. (Aline), Kristiansson, K. (Kati), Nuotio, M.-L. (Marja-Liisa), Kobl, M. (Michael), Grallert, H. (Harald), Dehghan, A. (Abbas), Kuningas, M. (Maris), Vries, P.S. (Paul) de, Bruijn, R.F.A.G. (Renée) de, Willems, S.M. (Sara), Heikkilä, K. (Kauko), Silventoinen, K. (Karri), Pietilainen, K.H. (Kirsi Hannele), Legry, V. (Vanessa), Giedraitis, V. (Vilmantas), Goumidi, L. (Louisa), Syvanen, A.C., Strauch, K. (Konstantin), Koenig, W. (Wolfgang), Lichtner, P. (Peter), Herder, C. (Christian), Palotie, A. (Aarno), Menni, C. (Cristina), Uitterlinden, A.G. (André), Kuulasmaa, K. (Kari), Havulinna, A.S. (Aki), Moreno, L. (Luis), Gonzalez-Gross, M. (Marcela), Evans, A. (Alun), Tregouet, D.-A. (David-Alexandre), Yarnell, J.W.G. (John W.), Virtamo, J. (Jarmo), Ferrieres, J. (Jean), Veronesi, G. (Giovanni), Perola, M. (Markus), Arveiler, D. (Dominique), Brambilla, P. (Paolo), Lind, L. (Lars), Kaprio, J. (Jaakko), Hofman, A. (Albert), Stricker, B.H.Ch. (Bruno), Duijn, C.M. (Cornelia) van, Ikram, M.A. (Arfan), Franco, O.H. (Oscar), Cottel, D. (Dominique), Dallongeville, J., Hall, A.S. (Alistair), Jula, A. (Antti), Tobin, M.D. (Martin), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Gieger, C. (Christian), Samani, N.J. (Nilesh), Montgomery, G.W. (Grant), Whitfield, J. (John), Martin, N.G. (Nicholas), Groop, L. (Leif), Spector, T.D. (Timothy), Magnusson, P.K. (Patrik), Amouyel, P. (Philippe), Boomsma, D.I. (Dorret), Nilsson, P. (Peter), Jarvelin, M.-R. (Marjo-Riitta), Lyssenko, V. (Valeriya), Metspalu, A. (Andres), Strachan, D.P. (David), Salomaa, V. (Veikko), Ripatti, S. (Samuli), Pedersen, N.L. (Nancy), Prokopenko, I. (Inga), McCarthy, M.I. (Mark), and Ingelsson, E. (Erik)
Abstract: Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
Published: 2015
Full Text: View/download PDF

45. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, P.K. (Peter), Esko, T. (Tõnu), Mattsson, H. (Hannele), Eklund, N. (Niina), Gandin, I. (Ilaria), Nutile, T., Jackson, A.U. (Anne), Schurmann, C. (Claudia), Smith, A.V. (Davey), Zhang, W. (Weihua), Okada, Y. (Yukinori), Stancáková, A. (Alena), Faul, J.D. (Jessica D.), Zhao, W. (Wei), Bartz, T.M. (Traci M.), Concas, M.P. (Maria Pina), Franceschini, N. (Nora), Enroth, S. (Stefan), Vitart, V. (Veronique), Trompet, S. (Stella), Guo, X. (Xiuqing), Chasman, D.I. (Daniel), O'Connel, J.R. (Jeffrey R.), Corre, T. (Tanguy), Nongmaithem, S.S. (Suraj S.), Chen, Y. (Yuning), Mangino, M. (Massimo), Ruggiero, D., Traglia, M. (Michela), Farmaki, A.-E. (Aliki-Eleni), Kacprowski, T. (Tim), Bjonnes, A. (Andrew), Spek, A. (Ashley) van der, Wu, Y. (Ying), Giri, A.K. (Anil K.), Yanek, L.R. (Lisa), Wang, L. (Lihua), Hofer, E. (Edith), Rietveld, C.A. (Niels), McLeod, O. (Olga), Cornelis, M. (Marilyn), Pattaro, C. (Cristian), Verweij, N. (Niek), Baumbach, C. (Clemens), Abdellaoui, A. (Abdel), Warren, H. (Helen), Vuckovic, D. (Dragana), Mei, H. (Hao), Bouchard, C. (Claude), Perry, J.R.B. (John), Cappellani, S. (Stefania), Mirza, S.S. (Saira), Benton, M.C. (Miles C.), Broeckel, U. (Ulrich), Medland, S.E. (Sarah), Lind, P.A. (Penelope), Malerba, G. (Giovanni), Drong, A. (Alexander), Yengo, L. (Loic), Bielak, L.F. (Lawrence F.), Zhi, D. (Degui), Most, P.J. (Peter) van der, Shriner, D. (Daniel), Mägi, R. (Reedik), Hemani, G., Karaderi, T. (Tugce), Wang, Z. (Zhaoming), Liu, T. (Tian), Demuth, I. (Ilja), Zhao, J.H. (Jing Hua), Meng, W. (Weihua), Lataniotis, L. (Lazaros), Van Der Laan, S.W. (Sander W.), Bradfield, J.P. (Jonathan), Wood, A.R. (Andrew), Bonnefond, A. (Amélie), Ahluwalia, T.S. (Tarunveer Singh), Hall, L.M. (Leanne M.), Salvi, E. (Erika), Yazar, S. (Seyhan), Carstensen, L. (Lisbeth), Haan, H.G. (Hugoline) de, Abney, M. (Mark), Afzal, U. (Uzma), Allison, M.A. (Matthew), Amin, N. (Najaf), Asselbergs, F.W. (Folkert W.), Bakker, S.J.L. (Stephan), Barr, R.G. (Graham), Baumeister, S.E. (Sebastian), Benjamin, D.J. (Daniel J.), Bergmann, S. (Sven), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Campbell, A. (Archie), Chakravarti, A. (Aravinda), Chan, Y. (Yingleong), Chanock, S.J. (Stephen), Chen, C. (Constance), Chen, Y.-D.I. (Y.-D. Ida), Collins, F.S. (Francis), Connell, J. (John), Correa, A. (Adolfo), Cupples, L.A. (Adrienne), Davies, G. (Gail), Dörr, M. (Marcus), Ehret, G.B. (Georg), Ellis, S.B. (Stephen B.), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Ford, I., Fox, C.S. (Caroline), Frayling, T.M. (Timothy), Friedrich, N. (Nele), Geller, F. (Frank), Scotland, G. (Generation), Gillham-Nasenya, I. (Irina), Gottesman, R.F. (Rebecca), Graff, M.J. (Maud J.L.), Grodstein, F. (Francine), Gu, C. (Charles), Haley, C. (Chris), Hammond, C.J. (Christopher), Harris, S.E. (Sarah), Harris, T.B. (Tamara), Hastie, N. (Nick), Heard-Costa, N.L. (Nancy), Heikkilä, K. (Kauko), Hocking, L.J. (Lynne), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huffman, J.E. (Jennifer), Hysi, P.G. (Pirro), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Joensuu, A. (Anni), Johansson, A. (Åsa), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanoni, S. (Stavroula), Kerr, S.M. (Shona), Khan, N.M. (Nazir M.), Koellinger, Ph.D. (Philipp), Koistinen, H.A. (Heikki A.), Kooner, M.K. (Manraj K.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lahti, J. (Jari), Launer, L.J. (Lenore), Lea, R.A. (Rodney A.), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Lind, L. (Lars), Loh, M. (Marie), Lokki, M.L., London, S.J. (Stephanie J.), Loomis, S.J. (Stephanie J.), Loukola, A. (Anu), Lu, Y. (Yingchang), Lumley, T. (Thomas), Lundqvist, A. (Annamari), Männistö, S. (Satu), Marques-Vidal, P. (Pedro), Masciullo, C. (Corrado), Matchan, A. (Angela), Mathias, J. (Jasmine), Matsuda, K. (Koichi), Meigs, J.B. (James), Meisinger, C. (Christa), Meitinger, T. (Thomas), Menni, C. (Cristina), Mentch, F.D. (Frank), Mihailov, E. (Evelin), Milani, L. (Lili), Montasser, M.E. (May E.), Montgomery, G.W. (Grant), Morrison, A.C. (Alanna), Myers, R.H. (Richard), Nadukuru, R. (Rajiv), Navarro, P. (Pau), Nalis, M. (Mari), Nieminen, M.S. (Markku S.), Nolte, I.M. (Ilja M.), O'Connor, G.T. (George), Ogunniyi, A. (Adesola), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Pankow, J.S. (James), Patarcic, I. (Inga), Pavani, F. (Francesca), Peyser, P.A. (Patricia A.), Pietilainen, K.H. (Kirsi Hannele), Poulter, N.R. (Neil), Prokopenko, I. (Inga), Ralhan, S. (Sarju), Redmond, P. (Paul), Rich, S.S. (Stephen S.), Rissanen, H. (Harri), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rose, R.J. (Richard J.), Sala, C. (Cinzia), Salako, B. (Babatunde), Salomaa, V. (Veikko), Sarin, A.-P., Saxena, R. (Richa), Schmidt, R. (Reinhold), Scott, L.J. (Laura), Scott, W.R. (William R.), Sennblad, B. (Bengt), Seshadri, S. (Sudha), Sever, P. (Peter), Shrestha, S. (Smeeta), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Sotoodehnia, N. (Nona), Southam, L. (Lorraine), Stanton, A. (Alice), Stathopoulou, M.G. (Maria G), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Suderman, M.J. (Matthew J.), Tandon, N. (Nikhil), Tang, S.-T. (Sian-Tsun), Taylor, K.D. (Kent D.), Tayo, B. (Bamidele), Töglhofer, A.M. (Anna Maria), Tomaszewski, M. (Maciej), Tsernikova, N. (Natalia), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Hylckama Vlieg, A. (Astrid) van, Setten, J. (Jessica) van, Vasankari, T. (Tuula), Vedantam, S. (Sailaja), Vlachopoulou, E. (Efthymia), Vozzi, D. (Diego), Vuoksimaa, E. (Eero), Waldenberger, M. (Melanie), Ware, E.B. (Erin B.), Wentworth-Shields, W. (William), Whitfield, J. (John), Wild, S. (Sarah), Willemsen, G.A.H.M. (Gonneke), Yajnik, C.S. (Chittaranjan S.), Yao, J. (Jie), Zaza, G. (Gianluigi), Zhu, X. (Xiaofeng), Salem, R.M. (Rany), Melbye, M. (Mads), Bisgaard, H. (Hans), Samani, N.J. (Nilesh), Cusi, D. (Daniele), Mackey, D.A. (David A.), Cooper, R.S. (Richard S.), Froguel, P. (Philippe), Pasterkamp, G. (Gerard), Grant, S.F.A. (Struan F.A.), Hakonarson, H. (Hakon), Ferrucci, L. (Luigi), Scott, R.A. (Robert), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Dedoussis, G.V. (George V.), Deloukas, P. (Panagiotis), Bertram, L. (Lars), Lindenberger, U. (Ulman), Berndt, S.I. (Sonja), Lindgren, C.M. (Cecilia), Timpson, N.J. (Nicholas), Tönjes, A. (Anke), Munroe, P. (Patricia), Sørensen, T.I.A. (Thorkild I.A.), Rotimi, C. (Charles), Arnett, D.K. (Donna), Oldehinkel, A.J. (Albertine), Kardia, S.L.R. (Sharon), Balkau, B. (Beverley), Gambaro, G. (Giovanni), Morris, A.P. (Andrew), Eriksson, J.G. (Johan G.), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Hunt, S.C. (Steven), Starr, J.M. (John), Deary, I.J. (Ian), Griffiths, L.R. (Lyn R.), Tiemeier, H.W. (Henning), Pirastu, N. (Nicola), Kaprio, J. (Jaakko), Wareham, N.J. (Nick), Perusse, L. (Louis), Wilson, J.G. (James), Girotto, S., Caulfield, M. (Mark), Raitakari, O.T. (Olli T.), Boomsma, D.I. (Dorret), Gieger, C. (Christian), van der Harst, P., Hicks, A.A. (Andrew), Kraft, P. (Peter), Sinisalo, J. (Juha), Knekt, P., Johannesson, M. (Magnus), Magnusson, P.K.E. (Patrik K. E.), Hamsten, A. (Anders), Borecki, I.B. (Ingrid), Vartiainen, E. (Erkki), Becker, D.M. (Diane), Bharadwaj, D. (Dwaipayan), Mohlke, K.L. (Karen), Boehnke, M. (Michael), Duijn, C.M. (Cornelia) van, Sanghera, D.K. (Dharambir), Teumer, A. (Alexander), Zeggini, E. (Eleftheria), Metspalu, A. (Andres), Gasparini, P. (Paolo), Ulivi, S. (Shelia), Ober, C. (Carole), Toniolo, D. (Daniela), Rudan, I. (Igor), Porteous, D.J. (David J.), Ciullo, M., Spector, T.D. (Timothy), Hayward, C. (Caroline), Dupuis, J. (Josée), Loos, R.J.F. (Ruth), Wright, A. (Alan), Chandak, G.R. (Giriraj), Vollenweider, P. (Peter), Shuldiner, A.R. (Alan), Ridker, P.M. (Paul), Rotter, J.I. (Jerome I.), Sattar, N. (Naveed), Gyllensten, U. (Ulf), North, K.E. (Kari), Pirastu, M. (Mario), Psaty, B.M. (Bruce), Weir, D.R. (David), Laakso, M. (Markku), Gudnason, V. (Vilmundur), Takahashi, A. (Atsushi), Chambers, J.C. (John C.), Kooner, J.S. (Jaspal S.), Strachan, D.P. (David P.), Campbell, H. (Harry), Hirschhorn, J.N. (Joel N.), Perola, M. (Markus), Polasek, O. (Ozren), Wilson, J.F. (James), Joshi, P.K. (Peter), Esko, T. (Tõnu), Mattsson, H. (Hannele), Eklund, N. (Niina), Gandin, I. (Ilaria), Nutile, T., Jackson, A.U. (Anne), Schurmann, C. (Claudia), Smith, A.V. (Davey), Zhang, W. (Weihua), Okada, Y. (Yukinori), Stancáková, A. (Alena), Faul, J.D. (Jessica D.), Zhao, W. (Wei), Bartz, T.M. (Traci M.), Concas, M.P. (Maria Pina), Franceschini, N. (Nora), Enroth, S. (Stefan), Vitart, V. (Veronique), Trompet, S. (Stella), Guo, X. (Xiuqing), Chasman, D.I. (Daniel), O'Connel, J.R. (Jeffrey R.), Corre, T. (Tanguy), Nongmaithem, S.S. (Suraj S.), Chen, Y. (Yuning), Mangino, M. (Massimo), Ruggiero, D., Traglia, M. (Michela), Farmaki, A.-E. (Aliki-Eleni), Kacprowski, T. (Tim), Bjonnes, A. (Andrew), Spek, A. (Ashley) van der, Wu, Y. (Ying), Giri, A.K. (Anil K.), Yanek, L.R. (Lisa), Wang, L. (Lihua), Hofer, E. (Edith), Rietveld, C.A. (Niels), McLeod, O. (Olga), Cornelis, M. (Marilyn), Pattaro, C. (Cristian), Verweij, N. (Niek), Baumbach, C. (Clemens), Abdellaoui, A. (Abdel), Warren, H. (Helen), Vuckovic, D. (Dragana), Mei, H. (Hao), Bouchard, C. (Claude), Perry, J.R.B. (John), Cappellani, S. (Stefania), Mirza, S.S. (Saira), Benton, M.C. (Miles C.), Broeckel, U. (Ulrich), Medland, S.E. (Sarah), Lind, P.A. (Penelope), Malerba, G. (Giovanni), Drong, A. (Alexander), Yengo, L. (Loic), Bielak, L.F. (Lawrence F.), Zhi, D. (Degui), Most, P.J. (Peter) van der, Shriner, D. (Daniel), Mägi, R. (Reedik), Hemani, G., Karaderi, T. (Tugce), Wang, Z. (Zhaoming), Liu, T. (Tian), Demuth, I. (Ilja), Zhao, J.H. (Jing Hua), Meng, W. (Weihua), Lataniotis, L. (Lazaros), Van Der Laan, S.W. (Sander W.), Bradfield, J.P. (Jonathan), Wood, A.R. (Andrew), Bonnefond, A. (Amélie), Ahluwalia, T.S. (Tarunveer Singh), Hall, L.M. (Leanne M.), Salvi, E. (Erika), Yazar, S. (Seyhan), Carstensen, L. (Lisbeth), Haan, H.G. (Hugoline) de, Abney, M. (Mark), Afzal, U. (Uzma), Allison, M.A. (Matthew), Amin, N. (Najaf), Asselbergs, F.W. (Folkert W.), Bakker, S.J.L. (Stephan), Barr, R.G. (Graham), Baumeister, S.E. (Sebastian), Benjamin, D.J. (Daniel J.), Bergmann, S. (Sven), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Campbell, A. (Archie), Chakravarti, A. (Aravinda), Chan, Y. (Yingleong), Chanock, S.J. (Stephen), Chen, C. (Constance), Chen, Y.-D.I. (Y.-D. Ida), Collins, F.S. (Francis), Connell, J. (John), Correa, A. (Adolfo), Cupples, L.A. (Adrienne), Davies, G. (Gail), Dörr, M. (Marcus), Ehret, G.B. (Georg), Ellis, S.B. (Stephen B.), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Ford, I., Fox, C.S. (Caroline), Frayling, T.M. (Timothy), Friedrich, N. (Nele), Geller, F. (Frank), Scotland, G. (Generation), Gillham-Nasenya, I. (Irina), Gottesman, R.F. (Rebecca), Graff, M.J. (Maud J.L.), Grodstein, F. (Francine), Gu, C. (Charles), Haley, C. (Chris), Hammond, C.J. (Christopher), Harris, S.E. (Sarah), Harris, T.B. (Tamara), Hastie, N. (Nick), Heard-Costa, N.L. (Nancy), Heikkilä, K. (Kauko), Hocking, L.J. (Lynne), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huffman, J.E. (Jennifer), Hysi, P.G. (Pirro), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Joensuu, A. (Anni), Johansson, A. (Åsa), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanoni, S. (Stavroula), Kerr, S.M. (Shona), Khan, N.M. (Nazir M.), Koellinger, Ph.D. (Philipp), Koistinen, H.A. (Heikki A.), Kooner, M.K. (Manraj K.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lahti, J. (Jari), Launer, L.J. (Lenore), Lea, R.A. (Rodney A.), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Lind, L. (Lars), Loh, M. (Marie), Lokki, M.L., London, S.J. (Stephanie J.), Loomis, S.J. (Stephanie J.), Loukola, A. (Anu), Lu, Y. (Yingchang), Lumley, T. (Thomas), Lundqvist, A. (Annamari), Männistö, S. (Satu), Marques-Vidal, P. (Pedro), Masciullo, C. (Corrado), Matchan, A. (Angela), Mathias, J. (Jasmine), Matsuda, K. (Koichi), Meigs, J.B. (James), Meisinger, C. (Christa), Meitinger, T. (Thomas), Menni, C. (Cristina), Mentch, F.D. (Frank), Mihailov, E. (Evelin), Milani, L. (Lili), Montasser, M.E. (May E.), Montgomery, G.W. (Grant), Morrison, A.C. (Alanna), Myers, R.H. (Richard), Nadukuru, R. (Rajiv), Navarro, P. (Pau), Nalis, M. (Mari), Nieminen, M.S. (Markku S.), Nolte, I.M. (Ilja M.), O'Connor, G.T. (George), Ogunniyi, A. (Adesola), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Pankow, J.S. (James), Patarcic, I. (Inga), Pavani, F. (Francesca), Peyser, P.A. (Patricia A.), Pietilainen, K.H. (Kirsi Hannele), Poulter, N.R. (Neil), Prokopenko, I. (Inga), Ralhan, S. (Sarju), Redmond, P. (Paul), Rich, S.S. (Stephen S.), Rissanen, H. (Harri), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rose, R.J. (Richard J.), Sala, C. (Cinzia), Salako, B. (Babatunde), Salomaa, V. (Veikko), Sarin, A.-P., Saxena, R. (Richa), Schmidt, R. (Reinhold), Scott, L.J. (Laura), Scott, W.R. (William R.), Sennblad, B. (Bengt), Seshadri, S. (Sudha), Sever, P. (Peter), Shrestha, S. (Smeeta), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Sotoodehnia, N. (Nona), Southam, L. (Lorraine), Stanton, A. (Alice), Stathopoulou, M.G. (Maria G), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Suderman, M.J. (Matthew J.), Tandon, N. (Nikhil), Tang, S.-T. (Sian-Tsun), Taylor, K.D. (Kent D.), Tayo, B. (Bamidele), Töglhofer, A.M. (Anna Maria), Tomaszewski, M. (Maciej), Tsernikova, N. (Natalia), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Hylckama Vlieg, A. (Astrid) van, Setten, J. (Jessica) van, Vasankari, T. (Tuula), Vedantam, S. (Sailaja), Vlachopoulou, E. (Efthymia), Vozzi, D. (Diego), Vuoksimaa, E. (Eero), Waldenberger, M. (Melanie), Ware, E.B. (Erin B.), Wentworth-Shields, W. (William), Whitfield, J. (John), Wild, S. (Sarah), Willemsen, G.A.H.M. (Gonneke), Yajnik, C.S. (Chittaranjan S.), Yao, J. (Jie), Zaza, G. (Gianluigi), Zhu, X. (Xiaofeng), Salem, R.M. (Rany), Melbye, M. (Mads), Bisgaard, H. (Hans), Samani, N.J. (Nilesh), Cusi, D. (Daniele), Mackey, D.A. (David A.), Cooper, R.S. (Richard S.), Froguel, P. (Philippe), Pasterkamp, G. (Gerard), Grant, S.F.A. (Struan F.A.), Hakonarson, H. (Hakon), Ferrucci, L. (Luigi), Scott, R.A. (Robert), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Dedoussis, G.V. (George V.), Deloukas, P. (Panagiotis), Bertram, L. (Lars), Lindenberger, U. (Ulman), Berndt, S.I. (Sonja), Lindgren, C.M. (Cecilia), Timpson, N.J. (Nicholas), Tönjes, A. (Anke), Munroe, P. (Patricia), Sørensen, T.I.A. (Thorkild I.A.), Rotimi, C. (Charles), Arnett, D.K. (Donna), Oldehinkel, A.J. (Albertine), Kardia, S.L.R. (Sharon), Balkau, B. (Beverley), Gambaro, G. (Giovanni), Morris, A.P. (Andrew), Eriksson, J.G. (Johan G.), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Hunt, S.C. (Steven), Starr, J.M. (John), Deary, I.J. (Ian), Griffiths, L.R. (Lyn R.), Tiemeier, H.W. (Henning), Pirastu, N. (Nicola), Kaprio, J. (Jaakko), Wareham, N.J. (Nick), Perusse, L. (Louis), Wilson, J.G. (James), Girotto, S., Caulfield, M. (Mark), Raitakari, O.T. (Olli T.), Boomsma, D.I. (Dorret), Gieger, C. (Christian), van der Harst, P., Hicks, A.A. (Andrew), Kraft, P. (Peter), Sinisalo, J. (Juha), Knekt, P., Johannesson, M. (Magnus), Magnusson, P.K.E. (Patrik K. E.), Hamsten, A. (Anders), Borecki, I.B. (Ingrid), Vartiainen, E. (Erkki), Becker, D.M. (Diane), Bharadwaj, D. (Dwaipayan), Mohlke, K.L. (Karen), Boehnke, M. (Michael), Duijn, C.M. (Cornelia) van, Sanghera, D.K. (Dharambir), Teumer, A. (Alexander), Zeggini, E. (Eleftheria), Metspalu, A. (Andres), Gasparini, P. (Paolo), Ulivi, S. (Shelia), Ober, C. (Carole), Toniolo, D. (Daniela), Rudan, I. (Igor), Porteous, D.J. (David J.), Ciullo, M., Spector, T.D. (Timothy), Hayward, C. (Caroline), Dupuis, J. (Josée), Loos, R.J.F. (Ruth), Wright, A. (Alan), Chandak, G.R. (Giriraj), Vollenweider, P. (Peter), Shuldiner, A.R. (Alan), Ridker, P.M. (Paul), Rotter, J.I. (Jerome I.), Sattar, N. (Naveed), Gyllensten, U. (Ulf), North, K.E. (Kari), Pirastu, M. (Mario), Psaty, B.M. (Bruce), Weir, D.R. (David), Laakso, M. (Markku), Gudnason, V. (Vilmundur), Takahashi, A. (Atsushi), Chambers, J.C. (John C.), Kooner, J.S. (Jaspal S.), Strachan, D.P. (David P.), Campbell, H. (Harry), Hirschhorn, J.N. (Joel N.), Perola, M. (Markus), Polasek, O. (Ozren), and Wilson, J.F. (James)
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been p
Published: 2015
Full Text: View/download PDF

46. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author: Loth, D.W. (Daan), Artigas, M.S., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Davey), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David), James, A.L. (Alan), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nick), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna), Thyagarajan, B. (Bharat), Alves, A.C. (Alexessander Couto), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), Vonk, J.M. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S.H. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome), Gao, W. (Wei), Postma, D.S. (Dirkje), White, W.B. (Wendy), Rich, S.S. (Stephen), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D. (David), Smith, L.J. (Lewis), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.W. (Arthur), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), O'Connor, G.T. (George), Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan), Starr, J.M. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher), Burkart, K.M. (Kristin), Beilby, J.P. (John), Kritchevsky, S.B. (Stephen), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O.D. (Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Jong, K.T. (Kim) de, Wjst, M. (Matthias), Kim, W.H. (Woo), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne), Jarvelin, M.-R. (Marjo-Riitta), Wilson, J.F. (James), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), Verhamme, F.M. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), London, S.J. (Stephanie), Loth, D.W. (Daan), Artigas, M.S., Gharib, S.A. (Sina), Wain, L.V. (Louise), Franceschini, N. (Nora), Koch, B. (Beate), Pottinger, T.D. (Tess), Smith, A.V. (Davey), Duan, Q. (Qing), Oldmeadow, C. (Christopher), Lee, M.K. (Mi Kyeong), Strachan, D.P. (David), James, A.L. (Alan), Huffman, J.E. (Jennifer), Vitart, V. (Veronique), Ramasamy, A. (Adaikalavan), Wareham, N.J. (Nick), Kaprio, J. (Jaakko), Wang, X.-Q. (Xin-Qun), Trochet, H. (Holly), Kähönen, M. (Mika), Flexeder, C. (Claudia), Albrecht, E. (Eva), Lopez, L.M. (Lorna), Thyagarajan, B. (Bharat), Alves, A.C. (Alexessander Couto), Enroth, S. (Stefan), Omenaas, E. (Ernst), Joshi, P.K. (Peter), Fall, M. (Magnus), Viñuela, A. (Ana), Launer, L.J. (Lenore), Loehr, L.R. (Laura), Fornage, M. (Myriam), Li, G. (Guo), Wilk, J.B. (Jemma), Tang, W. (Wenbo), Manichaikul, A. (Ani), Lahousse, L. (Lies), Harris, T.B. (Tamara), North, K.E. (Kari), Rudnicka, A.R. (Alicja), Hui, J. (Jennie), Gu, X. (Xiangjun), Lumley, T. (Thomas), Wright, A.F. (Alan), Hastie, N. (Nick), Campbell, S. (Susan), Kumar, R. (Rajesh), Pin, I. (Isabelle), Scott, R.A. (Robert), Pietilainen, K.H. (Kirsi Hannele), Surakka, I. (Ida), Liu, Y. (YongMei), Holliday, E.G. (Elizabeth), Schulz, H. (Holger), Heinrich, J. (Joachim), Davies, G. (Gail), Vonk, J.M. (Judith), Wojczynski, M.K. (Mary ), Pouta, A. (Anneli), Johansson, A. (Åsa), Wild, S.H. (Sarah), Ingelsson, E. (Erik), Rivadeneira Ramirez, F. (Fernando), Völzke, H. (Henry), Hysi, P.G. (Pirro), Eiriksdottir, G. (Gudny), Morrison, A.C. (Alanna), Rotter, J.I. (Jerome), Gao, W. (Wei), Postma, D.S. (Dirkje), White, W.B. (Wendy), Rich, S.S. (Stephen), Hofman, A. (Albert), Aspelund, T. (Thor), Couper, D. (David), Smith, L.J. (Lewis), Psaty, B.M. (Bruce), Lohman, K. (Kurt), Burchard, E.G. (Esteban), Uitterlinden, A.G. (André), Garcia, M. (Melissa), Joubert, B.R. (Bonnie), McArdle, W.L. (Wendy), Musk, A.W. (Arthur), Hansel, C.R.W. (Christian), Heckbert, S.R. (Susan), Zgaga, L. (Lina), Meurs, J.B.J. (Joyce) van, Navarro, P. (Pau), Rudan, I. (Igor), Oh, Y.-M. (Yeon-Mok), Redline, S. (Susan), Jarvis, D.L. (Deborah), Zhao, J.H. (Jing Hua), Rantanen, T. (Taina), O'Connor, G.T. (George), Ripatti, S. (Samuli), Scott, R.J. (Rodney), Karrasch, S. (Stefan), Grallert, H. (Harald), Gaddis, N.C. (Nathan), Starr, J.M. (John), Wijmenga, C. (Cisca), Minster, R.L. (Ryan), Lederer, C.W. (Carsten), Pekkanen, J. (Juha), Gyllensten, U. (Ulf), Campbell, H. (Harry), Morris, A.P. (Andrew), Gläser, S. (Sven), Hammond, C.J. (Christopher), Burkart, K.M. (Kristin), Beilby, J.P. (John), Kritchevsky, S.B. (Stephen), Gudnason, V. (Vilmundur), Hancock, D.B. (Dana), Williams, O.D. (Dale), Polasek, O. (Ozren), Zemunik, T. (Tatijana), Kolcic, I. (Ivana), Petrini, M.F. (Marcy), Jong, K.T. (Kim) de, Wjst, M. (Matthias), Kim, W.H. (Woo), Porteous, D.J. (David J.), Scotland, G. (Generation), Smith, B.H. (Blair), Viljanen, A. (Anne), Heliovaara, M. (Markku), Attia, J. (John), Sayers, I. (Ian), Hampel, R. (Regina), Gieger, C. (Christian), Deary, I.J. (Ian), Boezen, H.M. (Marike), Newman, A.B. (Anne), Jarvelin, M.-R. (Marjo-Riitta), Wilson, J.F. (James), Lind, L. (Lars), Stricker, B.H.Ch. (Bruno), Teumer, A. (Alexander), Spector, T.D. (Timothy), Melén, E. (Erik), Peters, M.J. (Marjolein), Lange, L.A. (Leslie), Barr, R.G. (Graham), Bracke, K.R. (Ken), Verhamme, F.M. (Fien), Sung, J. (Joohon), Hiemstra, P.S. (Pieter), Cassano, P.A. (Patricia), Sood, A. (Akshay), Hayward, C. (Caroline), Dupuis, J. (Josée), Hall, I.P. (Ian), Brusselle, G.G. (Guy), Tobin, M.D. (Martin), and London, S.J. (Stephanie)
Abstract: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
Published: 2014
Full Text: View/download PDF

47. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory

Author: Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
Abstract: Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
Published: 2014
Full Text: View/download PDF

48. A common biological basis of obesity and nicotine addiction

Author: Thorgeirsson, T.E. (Thorgeir), Gudbjartsson, D.F. (Daniel), Sulem, P. (Patrick), Besenbacher, S. (Søren), Styrkarsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Walters, G.B. (Bragi), Furberg, H. (Helena), Sullivan, P. (Patrick), Marchini, J. (Jonathan), McCarthy, M.I. (M.), Steinthorsdottir, V. (Valgerdur), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Surakka, I. (Ida), Vink, J.M. (Jacqueline), Amin, N. (Najaf), Geller, F. (Frank), Rafnar, T. (Thorunn), Esko, T. (Tõnu), Walter, S. (Stefan), Gieger, C. (Christian), Rawal, R. (Rajesh), Mangino, M. (Massimo), Prokopenko, I. (Inga), Mägi, R. (Reedik), Keskitalo, K. (Kaisu), Gudjonsdottir, I.H. (Iris), Gretarsdottir, S. (Solveig), Stefansson, H. (Hreinn), Aulchenko, Y.S. (Yurii), Nelis, M. (Mari), Aben, K.K.H. (Katja), Heijer, M. (Martin) den, Soranzo, N. (Nicole), Valdes, A.M. (Ana Maria), Steves, C.J. (Claire), Uitterlinden, A.G. (André), Hofman, A. (Albert), Tönjes, A. (Anke), Kovacs, P. (Peter), Hottenga, J.J. (Jouke Jan), Willemsen, G.A.H.M. (Gonneke), Vogelzangs, N. (Nicole), Döring, A. (Angela), Dahmen, N. (N.), Nitz, B. (Barbara), Ripatti, S. (Samuli), Perola, M. (Markus), Kettunen, J. (Johannes), Hartikainen, A.L., Pouta, A. (Anneli), Laitinen, J. (Jaana), Isohanni, M.K. (Matti), Huei-Yi, S. (Shen), Allen, M. (Maxine), Krestyaninova, M. (Maria), Hall, A. (Anne), Thompson, J.R. (John), Oskarsson, H. (Hogni), Tyrfingsson, T. (Thorarinn), Kiemeney, L.A.L.M. (Bart), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Stumvoll, M. (Michael), Spector, T.D. (Timothy), Wichmann, H.E. (Heinz Erich), Metspalu, A. (Andres), Samani, N.J. (Nilesh), Penninx, B.W.J.H. (Brenda), Oostra, B.A. (Ben), Boomsma, D.I. (Dorret), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Kaprio, J. (Jaakko), Gulcher, J.R. (Jeffrey), Kim, Y. (Yunjung), Dackor, J. (Jennifer), Boerwinkle, E.A. (Eric), Franceschini, N. (Nora), Ardissino, D. (Diego), Bernardinelli, L. (Luisa), Mannucci, P.M. (Pier), Mauri, F. (Francesco), Merlini, P.A. (Piera), Absher, D. (Devin), Assimes, T.L. (Themistocles), Fortmann, S.P. (Stephen), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Quertermous, T. (Thomas), Ferrucci, L. (Luigi), Tanaka, T. (Toshiko), Bis, J.C. (Joshua), Haritunians, T. (Talin), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Thacker, E.L. (Evan), Almgren, P. (Peter), Groop, L. (Leif), Ladenvall, C. (Claes), Boehnke, M. (Michael), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Stringham, H.M. (Heather), Tuomilehto, J. (Jaakko), Benjamin, E.J. (Emelia), Hwang, S.J., Levy, D. (Daniel), Preis, S.R., Vasan, R.S. (Ramachandran Srini), Duan, J. (Jubao), Gejman, P.V. (Pablo), Levinson, D.F. (Douglas), Sanders, A.R. (Alan), Shi, J. (Jianxin), Lips, E.H. (Esther), McKay, J.D. (James), Agudo, A. (Antonio), Barzan, L. (Luigi), Bencko, V. (Vladimir), Benhamou, S. (Simone), Castellsagué, X. (Xavier), Canova, C. (Cristina), Conway, D.I. (David), Fabianova, E. (Eleonora), Foretova, L. (Lenka), Janout, V. (Vladimir), Healy, C.M. (Claire), Holcátová, I. (Ivana), Kjaerheim, K. (Kristina), Lagiou, P., Lissowska, J. (Jolanta), Lowry, R. (Ray), MacFarlane, T.V. (Tatiana), Mates, D. (Dana), Richiardi, L. (Lorenzo), Rudnai, P. (Peter), Szeszenia-Dabrowska, N. (Neonilia), Zaridze, D., Znaor, A. (Ariana), Lathrop, M. (Mark), Brennan, P. (Paul), Bandinelli, S. (Stefania), Frayling, T.M. (Timothy), Guralnik, J.M. (Jack), Milaneschi, Y. (Yuri), Perry, J.R.B. (John), Altshuler, D. (David), Elosua, R. (Roberto), Kathiresan, S. (Sekar), Lucas, G. (Gavin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Voight, B.F. (Benjamin), Smith, A.V. (Davey), Geus, E.J.C. (Eco) de, Chanock, S.J. (Stephen), Gu, F. (Fangyi), Hankinson, S.E. (Susan), Hunter, D. (David), Chasman, D.I. (Daniel), Everett, B.M. (Brendan), Paré, G. (Guillaume), Ridker, P.M. (Paul), Li, M.D. (Ming), Maes, H.H. (Hermine), Audrain-Mcgovern, J. (Janet), Posthuma, D. (Danielle), Thornton, L.M. (Laura), Lerman, C. (Caryn), Rose, J.E. (Jed), Ioannidis, J.P.A. (John), Kraft, P. (Peter), Lin, D.Y. (Dan), Liu, J. (Jason), Muglia, P. (Pierandrea), Waterworth, D. (Dawn), Pillai, A.D. (Ajay), Middleton, L. (Lefkos), Berrettini, W. (Wade), Knouff, C.W. (Christopher), Yuan, X. (Xin), Waeber, G. (Gérard), Vollenweider, P. (Peter), Preisig, M. (Martin), Wareham, N.J. (Nick), Zhao, J.H. (Jing Hua), Loos, R.J.F. (Ruth), Barroso, I.E. (Inês), Khaw, K-T. (Kay-Tee), Grundy, S.M. (Scott), Barter, P. (Phil), Mahley, R. (Robert), Kesaniemi, Y.A. (Antero), McPherson, R. (Ruth), Vincent, J. (John), Strauss, J.S. (John S), Kennedy, J. (James), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Day, R.N. (Richard), Matthews, K. (Keith), Bakke, A.B. (Arnold B.), Gulsvik, A. (Amund), Lucae, S. (Susanne), Ising, M. (Marcus), Brueckl, T. (Tanja), Horstmann, S. (Sonja), Heinrich, J. (Joachim), Lamina, C. (Claudia), Polasek, O. (Ozren), Zgaga, L. (Lina), Huffman, J.E. (Jennifer), Campbell, S. (Susan), Kooner, J.S. (Jaspal), Chambers, J.C. (John), Burnett, M.S., Devaney, J. (Joseph), Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Epstein, S.E. (Stephen), Wilson, J.F. (James), Wild, S.H. (Sarah), Campbell, H. (Harry), Vitart, V. (Veronique), Reilly, M.P. (Muredach), Li, M. (Mingyao), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Franke, A. (Andre), Wittig, M. (Michael), Schäfer, A. (Arne), Uda, M. (Manuela), Terracciano, A., Xiao, X. (Xiangjun), Busonero, F., Scheet, P. (Paul), Schlessinger, D., Clair, D.S., Rujescu, D. (Dan), Abecasis, G.R. (Gonçalo), Grabe, H.J. (Hans Jörgen), Teumer, A. (Alexander), Völzke, H. (Henry), Petersmann, A. (Astrid), John, U. (Ulrich), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Kolcic, I. (Ivana), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), Anderson, C. (Carl), Ahmed, T. (Tariq), Mathew, J. (Joseph), Parkes, M. (Miles), Satsangi, J. (Jack), Caulfield, M. (Mark), Munroe, P. (Patricia), Farrall, M. (Martin), Dominiczak, A. (Anna), Worthington, H. (Helen), Thomson, W. (Wendy), Eyre, D.S. (Dylan Samuel), Barton, A. (Anne), Mooser, V. (Vincent), Francks, C. (Clyde), Thorgeirsson, T.E. (Thorgeir), Gudbjartsson, D.F. (Daniel), Sulem, P. (Patrick), Besenbacher, S. (Søren), Styrkarsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Walters, G.B. (Bragi), Furberg, H. (Helena), Sullivan, P. (Patrick), Marchini, J. (Jonathan), McCarthy, M.I. (M.), Steinthorsdottir, V. (Valgerdur), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Surakka, I. (Ida), Vink, J.M. (Jacqueline), Amin, N. (Najaf), Geller, F. (Frank), Rafnar, T. (Thorunn), Esko, T. (Tõnu), Walter, S. (Stefan), Gieger, C. (Christian), Rawal, R. (Rajesh), Mangino, M. (Massimo), Prokopenko, I. (Inga), Mägi, R. (Reedik), Keskitalo, K. (Kaisu), Gudjonsdottir, I.H. (Iris), Gretarsdottir, S. (Solveig), Stefansson, H. (Hreinn), Aulchenko, Y.S. (Yurii), Nelis, M. (Mari), Aben, K.K.H. (Katja), Heijer, M. (Martin) den, Soranzo, N. (Nicole), Valdes, A.M. (Ana Maria), Steves, C.J. (Claire), Uitterlinden, A.G. (André), Hofman, A. (Albert), Tönjes, A. (Anke), Kovacs, P. (Peter), Hottenga, J.J. (Jouke Jan), Willemsen, G.A.H.M. (Gonneke), Vogelzangs, N. (Nicole), Döring, A. (Angela), Dahmen, N. (N.), Nitz, B. (Barbara), Ripatti, S. (Samuli), Perola, M. (Markus), Kettunen, J. (Johannes), Hartikainen, A.L., Pouta, A. (Anneli), Laitinen, J. (Jaana), Isohanni, M.K. (Matti), Huei-Yi, S. (Shen), Allen, M. (Maxine), Krestyaninova, M. (Maria), Hall, A. (Anne), Thompson, J.R. (John), Oskarsson, H. (Hogni), Tyrfingsson, T. (Thorarinn), Kiemeney, L.A.L.M. (Bart), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Stumvoll, M. (Michael), Spector, T.D. (Timothy), Wichmann, H.E. (Heinz Erich), Metspalu, A. (Andres), Samani, N.J. (Nilesh), Penninx, B.W.J.H. (Brenda), Oostra, B.A. (Ben), Boomsma, D.I. (Dorret), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Kaprio, J. (Jaakko), Gulcher, J.R. (Jeffrey), Kim, Y. (Yunjung), Dackor, J. (Jennifer), Boerwinkle, E.A. (Eric), Franceschini, N. (Nora), Ardissino, D. (Diego), Bernardinelli, L. (Luisa), Mannucci, P.M. (Pier), Mauri, F. (Francesco), Merlini, P.A. (Piera), Absher, D. (Devin), Assimes, T.L. (Themistocles), Fortmann, S.P. (Stephen), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Quertermous, T. (Thomas), Ferrucci, L. (Luigi), Tanaka, T. (Toshiko), Bis, J.C. (Joshua), Haritunians, T. (Talin), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Thacker, E.L. (Evan), Almgren, P. (Peter), Groop, L. (Leif), Ladenvall, C. (Claes), Boehnke, M. (Michael), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Stringham, H.M. (Heather), Tuomilehto, J. (Jaakko), Benjamin, E.J. (Emelia), Hwang, S.J., Levy, D. (Daniel), Preis, S.R., Vasan, R.S. (Ramachandran Srini), Duan, J. (Jubao), Gejman, P.V. (Pablo), Levinson, D.F. (Douglas), Sanders, A.R. (Alan), Shi, J. (Jianxin), Lips, E.H. (Esther), McKay, J.D. (James), Agudo, A. (Antonio), Barzan, L. (Luigi), Bencko, V. (Vladimir), Benhamou, S. (Simone), Castellsagué, X. (Xavier), Canova, C. (Cristina), Conway, D.I. (David), Fabianova, E. (Eleonora), Foretova, L. (Lenka), Janout, V. (Vladimir), Healy, C.M. (Claire), Holcátová, I. (Ivana), Kjaerheim, K. (Kristina), Lagiou, P., Lissowska, J. (Jolanta), Lowry, R. (Ray), MacFarlane, T.V. (Tatiana), Mates, D. (Dana), Richiardi, L. (Lorenzo), Rudnai, P. (Peter), Szeszenia-Dabrowska, N. (Neonilia), Zaridze, D., Znaor, A. (Ariana), Lathrop, M. (Mark), Brennan, P. (Paul), Bandinelli, S. (Stefania), Frayling, T.M. (Timothy), Guralnik, J.M. (Jack), Milaneschi, Y. (Yuri), Perry, J.R.B. (John), Altshuler, D. (David), Elosua, R. (Roberto), Kathiresan, S. (Sekar), Lucas, G. (Gavin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Voight, B.F. (Benjamin), Smith, A.V. (Davey), Geus, E.J.C. (Eco) de, Chanock, S.J. (Stephen), Gu, F. (Fangyi), Hankinson, S.E. (Susan), Hunter, D. (David), Chasman, D.I. (Daniel), Everett, B.M. (Brendan), Paré, G. (Guillaume), Ridker, P.M. (Paul), Li, M.D. (Ming), Maes, H.H. (Hermine), Audrain-Mcgovern, J. (Janet), Posthuma, D. (Danielle), Thornton, L.M. (Laura), Lerman, C. (Caryn), Rose, J.E. (Jed), Ioannidis, J.P.A. (John), Kraft, P. (Peter), Lin, D.Y. (Dan), Liu, J. (Jason), Muglia, P. (Pierandrea), Waterworth, D. (Dawn), Pillai, A.D. (Ajay), Middleton, L. (Lefkos), Berrettini, W. (Wade), Knouff, C.W. (Christopher), Yuan, X. (Xin), Waeber, G. (Gérard), Vollenweider, P. (Peter), Preisig, M. (Martin), Wareham, N.J. (Nick), Zhao, J.H. (Jing Hua), Loos, R.J.F. (Ruth), Barroso, I.E. (Inês), Khaw, K-T. (Kay-Tee), Grundy, S.M. (Scott), Barter, P. (Phil), Mahley, R. (Robert), Kesaniemi, Y.A. (Antero), McPherson, R. (Ruth), Vincent, J. (John), Strauss, J.S. (John S), Kennedy, J. (James), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Day, R.N. (Richard), Matthews, K. (Keith), Bakke, A.B. (Arnold B.), Gulsvik, A. (Amund), Lucae, S. (Susanne), Ising, M. (Marcus), Brueckl, T. (Tanja), Horstmann, S. (Sonja), Heinrich, J. (Joachim), Lamina, C. (Claudia), Polasek, O. (Ozren), Zgaga, L. (Lina), Huffman, J.E. (Jennifer), Campbell, S. (Susan), Kooner, J.S. (Jaspal), Chambers, J.C. (John), Burnett, M.S., Devaney, J. (Joseph), Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Epstein, S.E. (Stephen), Wilson, J.F. (James), Wild, S.H. (Sarah), Campbell, H. (Harry), Vitart, V. (Veronique), Reilly, M.P. (Muredach), Li, M. (Mingyao), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Franke, A. (Andre), Wittig, M. (Michael), Schäfer, A. (Arne), Uda, M. (Manuela), Terracciano, A., Xiao, X. (Xiangjun), Busonero, F., Scheet, P. (Paul), Schlessinger, D., Clair, D.S., Rujescu, D. (Dan), Abecasis, G.R. (Gonçalo), Grabe, H.J. (Hans Jörgen), Teumer, A. (Alexander), Völzke, H. (Henry), Petersmann, A. (Astrid), John, U. (Ulrich), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Kolcic, I. (Ivana), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), Anderson, C. (Carl), Ahmed, T. (Tariq), Mathew, J. (Joseph), Parkes, M. (Miles), Satsangi, J. (Jack), Caulfield, M. (Mark), Munroe, P. (Patricia), Farrall, M. (Martin), Dominiczak, A. (Anna), Worthington, H. (Helen), Thomson, W. (Wendy), Eyre, D.S. (Dylan Samuel), Barton, A. (Anne), Mooser, V. (Vincent), and Francks, C. (Clyde)
Abstract: Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34 216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10-7). These findings replicate in a second large data set (N=127 274, thereof 76 242 smokers) for both SI (P=1.2 × 10-5) and CPD (P=9.3 × 10-5). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.
Published: 2013
Full Text: View/download PDF

49. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Author: Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Prokopenko, I. (Inga), Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), and Prokopenko, I. (Inga)
Abstract: Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05).
Published: 2013
Full Text: View/download PDF

50. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment

Author: Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), Koellinger, Ph.D. (Philipp), Rietveld, C.A. (Niels), Medland, S.E. (Sarah), Derringer, J., Yang, J. (Joanna), Esko, T. (Tõnu), Martin, N.W. (Nicolas), Westra, H.J. (Harm-Jan), Shakhbazov, K. (Konstantin), Abdellaoui, A. (Abdel), Agrawal, A. (Arpana), Albrecht, E. (Eva), Alizadeh, B.Z. (Behrooz), Amin, N. (Najaf), Barnard, J. (John), Baumeister, S.E. (Sebastian), Benke, P.J. (Paul), Bielak, L.F. (Lawrence F.), Boatman, J.A. (Jeffrey), Boyle, P.A. (Patricia), Davies, G. (Gail), Leeuw, C. (Christiaan) de, Eklund, N. (Niina), Evans, D.S. (Daniel), Ferhmann, R. (Rudolf), Fischer, K. (Krista), Gieger, C. (Christian), Gjessing, H.K. (Håkon), Hägg, S. (Sara), Harris, J.R. (Jennifer), Hayward, C. (Caroline), Holzapfel, C. (Christina), Ibrahim-Verbaas, C.A. (Carla), Ingelsson, E. (Erik), Jacobsson, B. (Bo), Joshi, P.K. (Peter), Juqessur, A. (Astanand), Kaakinen, M. (Marika), Kanoni, S. (Stavroula), Karjalainen, J. (Juha), Kolcic, I. (Ivana), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Lahti, J. (Jari), Lee, S.H. (Sang Hong), Lin, P. (Peng), Lind, P.A. (Penelope), Liu, Y. (YongMei), Lohman, K. (Kurt), Loitfelder, M. (Marisa), Mcmahon, G. (George), Marques-Vidal, P. (Pedro), Meirelles, O., Milani, L. (Lili), Myhre, R. (Ronny), Nuotio, M.-L. (Marja-Liisa), Oldmeadow, C. (Christopher), Petrovic, K. (Katja), Peyrot, W.J. (Wouter ), Polasek, O. (Ozren), Quaye, L. (Lydia), Reinmaa, E. (Eva), Rice, J.P. (John), Rizzi, T.S. (Thais), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Tanaka, T. (Toshiko), Terracciano, A., Loos, M.J.H.M. (Matthijs) van der, Vitart, V. (Veronique), Völzke, H. (Henry), Wellmann, J. (Jürgen), Yu, L. (Lei), Zhao, W. (Wei), Allik, J., Attia, J. (John), Bandinelli, S. (Stefania), Bastardot, F. (Francois), Beauchamp, J.P. (Jonathan), Bennett, D.A. (David), Berger, K. (Klaus), Bierut, L.J. (Laura), Boomsma, D.I. (Dorret), Bültmann, U. (Ute), Campbell, H. (Harry), Chabris, C.F. (Christopher F.), Cherkas, L. (Lynn), Chung, M.K. (Mina), Cucca, F. (Francesco), Andrade, M. (Mariza) de, Jager, P.L. (Philip) de, Neve, J.E. (Jan-Emmanuel) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Dimitriou, M. (Maria), Eiríksdóttir, G. (Guoný), Elderson, M.F. (Martin), Eriksson, J.G. (Johan), Evans, D.M. (David), Faul, J.D. (Jessica), Ferrucci, L. (Luigi), Garcia, M. (Melissa), Grönberg, H. (Henrik), Guonason, V. (Vilmundur), Hall, P. (Per), Harris, J.M. (Juliette), Harris, T.B. (Tamara), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hoffmann, W. (Wolfgang), Holle, R. (Rolf), Holliday, E.G. (Elizabeth), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Kirkpatrick, R.M. (Robert), Kowgier, M. (Matthew), Latvala, A. (Antti), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Li, J. (Jingmei), Lichtenstein, P. (Paul), Lichtner, P. (Peter), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik), Mäkinen, T. (Tuukka), Masala, G. (Giovanna), McGue, M. (Matt), Metspalu, A. (Andres), Mielck, A. (Andreas), Miller, M. (Michael), Montgomery, G.W. (Grant), Mukherjee, S. (Sutapa), Nyholt, D.R. (Dale), Oostra, B.A. (Ben), Palmer, C. (Cameron), Palotie, A. (Aarno), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peyser, P.A. (Patricia A.), Preisig, M. (Martin), Räikkönen, K. (Katri), Raitakari, O. (Olli), Realo, A. (Anu), Ring, S.M. (Susan), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Rudan, I. (Igor), Rustichini, A. (Aldo), Salomaa, V. (Veikko), Sarin, A.-P., Schlessinger, D., Scott, R.J. (Rodney), Snieder, H. (Harold), St Pourcain, B. (Beate), Starr, J.M. (John), Sul, J.H. (Jae Hoon), Surakka, I. (Ida), Svento, R. (Rauli), Teumer, A. (Alexander), Tiemeier, H.W. (Henning), Rooij, F.J.A. (Frank) van, Wagoner, D.R. (David) van, Vartiainen, E. (Erkki), Viikari, J. (Jorma), Vollenweider, P. (Peter), Vonk, J.M. (Judith), Waeber, G. (Gérard), Weir, D.R. (David), Wichmann, H.E. (Heinz Erich), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (James), Wright, A.F. (Alan), Conley, D. (Dalton), Davey-Smith, G. (George), Franke, L. (Lude), Groenen, P.J.F. (Patrick), Hofman, A. (Albert), Johannesson, M. (Magnus), Kardia, S.L.R. (Sharon), Krueger, R.F., Laibson, D. (David), Martin, N.G. (Nicholas), Meyer, M.N. (Michelle), Posthuma, D. (Danielle), Thurik, A.R. (Roy), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Visscher, P.M. (Peter), Benjamin, D.J. (Daniel J.), Cesarini, D. (David), and Koellinger, Ph.D. (Philipp)
Published: 2013
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

69 results on '"Kaprio, J. (Jaakko)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources