Author: "Auer, P. (Paul)" - Searchworks@Jio Institute Digital Library Search Results

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1. 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

2. 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
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3. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits

Author: Pankratz, V.S. (Shane), Schick, U.M. (Ursula), Zhou, Y. (Yi), Zhou, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Allende, M.L. (Maria Laura), Auer, P. (Paul), Bork-Jensen, J. (Jette), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Clavo, V. (Vinna), Eicher, J.D. (John D.), Grarup, N. (Niels), Hagedorn, E.J. (Elliott J.), Hu, B. (Bella), Hunker, K. (Kristina), Johnson, A.D. (Andrew), Leusink, M. (Maarten), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Manichaikul, A. (Ani), Marioni, R.E. (Riccardo), Nalls, M.A. (Michael), Pazoki, R. (Raha), Smith, A.V. (Albert Vernon), Rooij, F.J.A. (Frank) van, Yang, M.-L. (Min-Lee), Zhang, X. (Xiaoling), Zhang, Y. (Yan), Asselbergs, F.W. (Folkert), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Bottinger, E.P. (Erwin), Cushman, M. (Mary Ann), Bakker, P.I.W. (Paul) de, Deary, I.J. (Ian), Dong, L. (Liguang), Feitosa, M.F. (Mary Furlan), Floyd, J. (James), Franceschini, N. (Nora), Franco, O.H. (Oscar), Garcia, M. (Melissa), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jia, J. (Jia), Kähönen, M. (Mika), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Nguyen, V.M. (Vy M.), Numans, M.E. (Mattijs), Pedersen, O. (Oluf), Psaty, B.M. (Bruce M.), Raitakari, O.T. (Olli T.), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Di Sant, A.M.R. (Amanda M. Rosa), Rotter, J.I. (Jerome I.), Starr, J.M. (John), Taylor, K.D. (Kent), Thuesen, B.H. (Betina Heinsbek), Tracy, R.P. (Russell), Uitterlinden, A.G. (André), Wang, J. (Jiansong), Wang, J. (Judy), Dehghan, A. (Abbas), Huo, Y. (Yong), Cupples, L.A. (Adrienne), Wilson, J.F. (James), Proia, R.L. (Richard L.), Zon, L.I. (Leonard), O'Donnell, C.J. (Christopher), Reiner, A.P. (Alex P.), Ganesh, S.K. (Santhi), Pankratz, V.S. (Shane), Schick, U.M. (Ursula), Zhou, Y. (Yi), Zhou, W. (Wei), Ahluwalia, T.S. (Tarunveer Singh), Allende, M.L. (Maria Laura), Auer, P. (Paul), Bork-Jensen, J. (Jette), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Clavo, V. (Vinna), Eicher, J.D. (John D.), Grarup, N. (Niels), Hagedorn, E.J. (Elliott J.), Hu, B. (Bella), Hunker, K. (Kristina), Johnson, A.D. (Andrew), Leusink, M. (Maarten), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Manichaikul, A. (Ani), Marioni, R.E. (Riccardo), Nalls, M.A. (Michael), Pazoki, R. (Raha), Smith, A.V. (Albert Vernon), Rooij, F.J.A. (Frank) van, Yang, M.-L. (Min-Lee), Zhang, X. (Xiaoling), Zhang, Y. (Yan), Asselbergs, F.W. (Folkert), Boerwinkle, E.A. (Eric), Borecki, I.B. (Ingrid), Bottinger, E.P. (Erwin), Cushman, M. (Mary Ann), Bakker, P.I.W. (Paul) de, Deary, I.J. (Ian), Dong, L. (Liguang), Feitosa, M.F. (Mary Furlan), Floyd, J. (James), Franceschini, N. (Nora), Franco, O.H. (Oscar), Garcia, M. (Melissa), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hofman, A. (Albert), Jackson, R.D. (Rebecca), Jia, J. (Jia), Kähönen, M. (Mika), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Nguyen, V.M. (Vy M.), Numans, M.E. (Mattijs), Pedersen, O. (Oluf), Psaty, B.M. (Bruce M.), Raitakari, O.T. (Olli T.), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Di Sant, A.M.R. (Amanda M. Rosa), Rotter, J.I. (Jerome I.), Starr, J.M. (John), Taylor, K.D. (Kent), Thuesen, B.H. (Betina Heinsbek), Tracy, R.P. (Russell), Uitterlinden, A.G. (André), Wang, J. (Jiansong), Wang, J. (Judy), Dehghan, A. (Abbas), Huo, Y. (Yong), Cupples, L.A. (Adrienne), Wilson, J.F. (James), Proia, R.L. (Richard L.), Zon, L.I. (Leonard), O'Donnell, C.J. (Christopher), Reiner, A.P. (Alex P.), and Ganesh, S.K. (Santhi)
Abstract: Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury.
Published: 2016
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4. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

Author: Chami, N. (Nathalie), Chen, M.-H. (Ming-Huei), Slater, A.J. (Andrew J.), Eicher, J.D. (John D.), Evangelou, E. (Evangelos), Tajuddin, S.M. (Salman M.), Love-Gregory, L. (Latisha), Kacprowski, T. (Tim), Schick, U.M. (Ursula), Nomura, A. (Akihiro), Giri, A. (Ayush), Lessard, S. (Samuel), Brody, J.A. (Jennifer A.), Schurmann, C. (Claudia), Pankratz, V.S. (Shane), Yanek, L.R. (Lisa), Manichaikul, A. (Ani), Pazoki, R. (Raha), Mihailov, E. (Evelin), Hill, W.D. (W. David), Raffield, L.M. (Laura M.), Burt, A.D. (Alastair), Bartz, T.M. (Traci M.), Becker, D.M. (Diane), Becker, L.C. (Lewis), Boerwinkle, E.A. (Eric), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), O'Donoghue, M.L. (Michelle L.), Crosslin, D.R. (David), de Denus, S. (Simon), Dubé, M.-P. (Marie-Pierre), Elliott, P. (Paul), Engström, G., Evans, M.K. (Michele), Floyd, J. (James), Fornage, M. (Myriam), Gao, H. (He), Greinacher, A. (Andreas), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hayward, C. (Caroline), Hernesniemi, J. (Jussi), Highland, H. (Heather), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Irvin, M.R. (Marguerite R.), Kähönen, M. (Mika), Lange, E.M. (Ethan), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Li, J. (Jin), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mägi, R. (Reedik), Mathias, J. (Jasmine), Melander, O. (Olle), Metspalu, A. (Andres), Mononen, K. (Kari), Nalls, M.A. (Michael), Nickerson, D.A. (Deborah), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), Orho-Melander, M. (Marju), Pedersen, O. (Oluf), Petersmann, A. (Astrid), Polfus, L. (Linda), Psaty, B.M. (Bruce), Raitakari, O.T. (Olli T.), Raitoharju, E. (Emma), Richard, M. (Melissa), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Schmidt, F. (Frank), Smith, A.V. (Albert Vernon), Starr, J.M. (John), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thuesen, B.H. (Betina H.), Torstenson, E.S. (Eric S.), Tracy, R.P. (Russell), Tzoulaki, I., Zakai, N.A. (Neil), Vacchi-Suzzi, C. (Caterina), Duijn, C.M. (Cornelia) van, Rooij, F.J.A. (Frank) van, Cushman, M. (Mary Ann), Deary, I.J. (Ian), Velez Edwards, D.R. (Digna R.), Vergnaud, A.-C. (Anne-Claire), Wallentin, L.C. (Lars), Waterworth, D. (Dawn), White, H.D. (Harvey D.), Wilson, J.F. (James), Zonderman, A.B., Kathiresan, S. (Sekar), Grarup, N. (Niels), Esko, T. (Tõnu), Loos, R.J.F. (Ruth), Lange, L.A. (Leslie), Faraday, N. (Nauder), Abumrad, N.A. (Nada A.), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Auer, P. (Paul), Johnson, A.D. (Andrew), Reiner, A. (Alexander), Lettre, G. (Guillaume), Chami, N. (Nathalie), Chen, M.-H. (Ming-Huei), Slater, A.J. (Andrew J.), Eicher, J.D. (John D.), Evangelou, E. (Evangelos), Tajuddin, S.M. (Salman M.), Love-Gregory, L. (Latisha), Kacprowski, T. (Tim), Schick, U.M. (Ursula), Nomura, A. (Akihiro), Giri, A. (Ayush), Lessard, S. (Samuel), Brody, J.A. (Jennifer A.), Schurmann, C. (Claudia), Pankratz, V.S. (Shane), Yanek, L.R. (Lisa), Manichaikul, A. (Ani), Pazoki, R. (Raha), Mihailov, E. (Evelin), Hill, W.D. (W. David), Raffield, L.M. (Laura M.), Burt, A.D. (Alastair), Bartz, T.M. (Traci M.), Becker, D.M. (Diane), Becker, L.C. (Lewis), Boerwinkle, E.A. (Eric), Bork-Jensen, J. (Jette), Bottinger, E.P. (Erwin), O'Donoghue, M.L. (Michelle L.), Crosslin, D.R. (David), de Denus, S. (Simon), Dubé, M.-P. (Marie-Pierre), Elliott, P. (Paul), Engström, G., Evans, M.K. (Michele), Floyd, J. (James), Fornage, M. (Myriam), Gao, H. (He), Greinacher, A. (Andreas), Gudnason, V. (Vilmundur), Hansen, T. (T.), Harris, T.B. (Tamara), Hayward, C. (Caroline), Hernesniemi, J. (Jussi), Highland, H. (Heather), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Irvin, M.R. (Marguerite R.), Kähönen, M. (Mika), Lange, E.M. (Ethan), Launer, L.J. (Lenore J.), Lehtimäki, T. (Terho), Li, J. (Jin), Liewald, D.C.M. (David), Linneberg, A. (Allan), Liu, Y. (YongMei), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mägi, R. (Reedik), Mathias, J. (Jasmine), Melander, O. (Olle), Metspalu, A. (Andres), Mononen, K. (Kari), Nalls, M.A. (Michael), Nickerson, D.A. (Deborah), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), Orho-Melander, M. (Marju), Pedersen, O. (Oluf), Petersmann, A. (Astrid), Polfus, L. (Linda), Psaty, B.M. (Bruce), Raitakari, O.T. (Olli T.), Raitoharju, E. (Emma), Richard, M. (Melissa), Rice, K.M. (Kenneth), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Schmidt, F. (Frank), Smith, A.V. (Albert Vernon), Starr, J.M. (John), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thuesen, B.H. (Betina H.), Torstenson, E.S. (Eric S.), Tracy, R.P. (Russell), Tzoulaki, I., Zakai, N.A. (Neil), Vacchi-Suzzi, C. (Caterina), Duijn, C.M. (Cornelia) van, Rooij, F.J.A. (Frank) van, Cushman, M. (Mary Ann), Deary, I.J. (Ian), Velez Edwards, D.R. (Digna R.), Vergnaud, A.-C. (Anne-Claire), Wallentin, L.C. (Lars), Waterworth, D. (Dawn), White, H.D. (Harvey D.), Wilson, J.F. (James), Zonderman, A.B., Kathiresan, S. (Sekar), Grarup, N. (Niels), Esko, T. (Tõnu), Loos, R.J.F. (Ruth), Lange, L.A. (Leslie), Faraday, N. (Nauder), Abumrad, N.A. (Nada A.), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Auer, P. (Paul), Johnson, A.D. (Andrew), Reiner, A. (Alexander), and Lettre, G. (Guillaume)
Abstract: Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10−10 for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10−8 for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribut
Published: 2016
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5. Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis

Author: Polfus, L.M. (Linda M.), Khajuria, R.K. (Rajiv K.), Schick, U.M. (Ursula), Pankratz, V.S. (Shane), Pazoki, R. (Raha), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Auer, P. (Paul), Floyd, J. (James), Huang, J. (Jian), Lange, L.A. (Leslie), Rooij, F.J.A. (Frank) van, Gibbs, R.A. (Richard), Metcalf, G.A. (Ginger A.), Muzny, D. (Donna), Veeraraghavan, N. (Narayanan), Walter, K. (Klaudia), Chen, L. (Lu), Yanek, L.R. (Lisa), Becker, L.C. (Lewis), Peloso, G.M. (Gina), Wakabayashi, A. (Aoi), Kals, M. (Mart), Metspalu, A. (Andres), Esko, T. (Tõnu), Fox, K. (Keolu), Wallace, R. (Robert), Franceshini, N. (Nora), Aleksic, N. (Nena), Rice, K.M. (Kenneth), Bartz, T.M. (Traci M.), Lyytikäinen, L.-P. (Leo-Pekka), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Raitakari, O.T. (Olli T.), Li-Gao, R. (Ruifang), Mook-Kanamori, D.O. (Dennis), Lettre, G. (Guillaume), Duijn, C.M. (Cornelia) van, Franco, O.H. (Oscar), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Uitterlinden, A.G. (André), Wilson, J.F. (James), Psaty, B.M. (Bruce), Soranzo, N. (Nicole), Dehghan, A. (Abbas), Boerwinkle, E.A. (Eric), Zhang, X. (Xiaoling), Johnson, A.D. (Andrew), O'Donnell, C.J. (Christopher), Johnsen, J.M. (Jill M.), Reiner, A. (Alexander), Ganesh, S.K. (Santhi), Sankaran, V.G. (Vijay G.), Polfus, L.M. (Linda M.), Khajuria, R.K. (Rajiv K.), Schick, U.M. (Ursula), Pankratz, V.S. (Shane), Pazoki, R. (Raha), Brody, J.A. (Jennifer A.), Chen, M.-H. (Ming-Huei), Auer, P. (Paul), Floyd, J. (James), Huang, J. (Jian), Lange, L.A. (Leslie), Rooij, F.J.A. (Frank) van, Gibbs, R.A. (Richard), Metcalf, G.A. (Ginger A.), Muzny, D. (Donna), Veeraraghavan, N. (Narayanan), Walter, K. (Klaudia), Chen, L. (Lu), Yanek, L.R. (Lisa), Becker, L.C. (Lewis), Peloso, G.M. (Gina), Wakabayashi, A. (Aoi), Kals, M. (Mart), Metspalu, A. (Andres), Esko, T. (Tõnu), Fox, K. (Keolu), Wallace, R. (Robert), Franceshini, N. (Nora), Aleksic, N. (Nena), Rice, K.M. (Kenneth), Bartz, T.M. (Traci M.), Lyytikäinen, L.-P. (Leo-Pekka), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Raitakari, O.T. (Olli T.), Li-Gao, R. (Ruifang), Mook-Kanamori, D.O. (Dennis), Lettre, G. (Guillaume), Duijn, C.M. (Cornelia) van, Franco, O.H. (Oscar), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Uitterlinden, A.G. (André), Wilson, J.F. (James), Psaty, B.M. (Bruce), Soranzo, N. (Nicole), Dehghan, A. (Abbas), Boerwinkle, E.A. (Eric), Zhang, X. (Xiaoling), Johnson, A.D. (Andrew), O'Donnell, C.J. (Christopher), Johnsen, J.M. (Jill M.), Reiner, A. (Alexander), Ganesh, S.K. (Santhi), and Sankaran, V.G. (Vijay G.)
Abstract: Circulating blood cell counts and indices are important indicators of hematopoietic function and a number of clinical parameters, such as blood oxygen-carrying capacity, inflammation, and hemostasis. By performing whole-exome sequence association analyses of hematologic quantitative traits in 15,459 community-dwelling individuals, followed by in silico replication in up to 52,024 independent samples, we identified two previously undescribed coding variants associated with lower platelet count: a common missense variant in CPS1 (rs1047891, MAF = 0.33, discovery + replication p = 6.38 × 10−10) and a rare synonymous variant in GFI1B (rs150813342, MAF = 0.009, discovery + replication p = 1.79 × 10−27). By performing CRISPR/Cas9 genome editing in hematopoietic cell lines and follow-up targeted knockdown experiments in primary human hematopoietic stem and progenitor cells, we demonstrate an alternative splicing mechanism by which the GFI1B rs150813342 variant suppresses formation of a GFI1B isoform that pref
Published: 2016
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6. Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author: Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), and Soranzo, N. (Nicole)
Abstract: Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.
Published: 2016
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7. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Author: Liu, C. (Chunyu), Kraja, A. (Aldi), Smith, J.A. (Jennifer A), Brody, J.A. (Jennifer A.), Franceschini, N. (Nora), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Lu, Y. (Yingchang), Weiss, S. (Stefan), Guo, X. (Xiuqing), Palmas, W. (Walter), Martin, L.W. (Lisa), Chen, Y.D. (Y.), Surendran, P. (Praveen), Drenos, F. (Fotios), Cook, J.P. (James P.), Auer, P. (Paul), Chu, A.Y. (Audrey), Giri, A. (Ayush), Zhao, W. (Wei), Jakobsdottir, M. (Margret), Lin, L.-A. (Li-An), Stafford, J.M. (Jeanette M.), Amin, N. (Najaf), Mei, H. (Hao), Yao, J. (Jiefen), Voorman, J.M. (Jeanine), Larson, M.G. (Martin), Grove, M.L. (Megan), Smith, A.V. (Albert Vernon), Hwang, S.J., Chen, H. (Han), Huan, T. (Tianxiao), Kosova, G. (Gulum), Stitziel, N.O. (Nathan), Kathiresan, S. (Sekar), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Deloukas, P. (Panagiotis), Li, M. (Man), Fuchsberger, C. (Christian), Pattaro, C. (Cristian), Gorski, M. (Mathias), Kooperberg, C. (Charles), Papanicolaou, G. (George), Rossouw, J.E. (Jacques E.), Faul, J.D. (Jessica D.), Kardia, S.L.R. (Sharon), Bouchard, C. (Claude), Raffel, L.J. (Leslie), Uitterlinden, A.G. (André G.), Franco, O.H. (Oscar), Vasan, R. (Ramachandran), O'Donnell, C.J. (Christopher), Taylor, K.D. (Kent), Liu, K.Y., Bottinger, E.P. (Erwin), Gottesman, R.F. (Rebecca), Daw, E.W. (E. Warwick), Giulianini, F. (Franco), Ganesh, S.K. (Santhi), Salfati, E. (Elias), Harris, T.B. (Tamara), Launer, L.J. (Lenore J.), Dörr, M. (Marcus), Felix, S.B. (Stephan), Rettig, R. (Rainer), Völzke, H. (Henry), Kim, E. (Eric), Lee, W.-J. (Wen-Jane), Lee, I.T., Sheu, W.H.-H. (Wayne H.-H.), Tsosie, K.S. (Krystal S.), Edwards, D.R.V. (Digna R. Velez), Liu, Y. (YongMei), Correa, A. (Adolfo), Weir, D.R. (David), Völker, U. (Uwe), Ridker, P.M. (Paul), Boerwinkle, E.A. (Eric), Gudnason, V. (Vilmundur), Reiner, A. (Alexander), Van Duijn, C.M. (Cornelia M.), Borecki, I.B. (Ingrid), Edwards, T.L. (Todd L.), Chakravarti, A. (Aravinda), Rotter, J.I. (Jerome I.), Psaty, B.M. (Bruce), Loos, R.J.F. (Ruth), Fornage, M. (Myriam), Ehret, G.B. (Georg), Newton-Cheh, C. (Christopher), Levy, D. (Daniel), Chasman, D.I. (Daniel), Liu, C. (Chunyu), Kraja, A. (Aldi), Smith, J.A. (Jennifer A), Brody, J.A. (Jennifer A.), Franceschini, N. (Nora), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Lu, Y. (Yingchang), Weiss, S. (Stefan), Guo, X. (Xiuqing), Palmas, W. (Walter), Martin, L.W. (Lisa), Chen, Y.D. (Y.), Surendran, P. (Praveen), Drenos, F. (Fotios), Cook, J.P. (James P.), Auer, P. (Paul), Chu, A.Y. (Audrey), Giri, A. (Ayush), Zhao, W. (Wei), Jakobsdottir, M. (Margret), Lin, L.-A. (Li-An), Stafford, J.M. (Jeanette M.), Amin, N. (Najaf), Mei, H. (Hao), Yao, J. (Jiefen), Voorman, J.M. (Jeanine), Larson, M.G. (Martin), Grove, M.L. (Megan), Smith, A.V. (Albert Vernon), Hwang, S.J., Chen, H. (Han), Huan, T. (Tianxiao), Kosova, G. (Gulum), Stitziel, N.O. (Nathan), Kathiresan, S. (Sekar), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Deloukas, P. (Panagiotis), Li, M. (Man), Fuchsberger, C. (Christian), Pattaro, C. (Cristian), Gorski, M. (Mathias), Kooperberg, C. (Charles), Papanicolaou, G. (George), Rossouw, J.E. (Jacques E.), Faul, J.D. (Jessica D.), Kardia, S.L.R. (Sharon), Bouchard, C. (Claude), Raffel, L.J. (Leslie), Uitterlinden, A.G. (André G.), Franco, O.H. (Oscar), Vasan, R. (Ramachandran), O'Donnell, C.J. (Christopher), Taylor, K.D. (Kent), Liu, K.Y., Bottinger, E.P. (Erwin), Gottesman, R.F. (Rebecca), Daw, E.W. (E. Warwick), Giulianini, F. (Franco), Ganesh, S.K. (Santhi), Salfati, E. (Elias), Harris, T.B. (Tamara), Launer, L.J. (Lenore J.), Dörr, M. (Marcus), Felix, S.B. (Stephan), Rettig, R. (Rainer), Völzke, H. (Henry), Kim, E. (Eric), Lee, W.-J. (Wen-Jane), Lee, I.T., Sheu, W.H.-H. (Wayne H.-H.), Tsosie, K.S. (Krystal S.), Edwards, D.R.V. (Digna R. Velez), Liu, Y. (YongMei), Correa, A. (Adolfo), Weir, D.R. (David), Völker, U. (Uwe), Ridker, P.M. (Paul), Boerwinkle, E.A. (Eric), Gudnason, V. (Vilmundur), Reiner, A. (Alexander), Van Duijn, C.M. (Cornelia M.), Borecki, I.B. (Ingrid), Edwards, T.L. (Todd L.), Chakravarti, A. (Aravinda), Rotter, J.I. (Jerome I.), Psaty, B.M. (Bruce), Loos, R.J.F. (Ruth), Fornage, M. (Myriam), Ehret, G.B. (Georg), Newton-Cheh, C. (Christopher), Levy, D. (Daniel), and Chasman, D.I. (Daniel)
Abstract: Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
Published: 2016
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8. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Author: Eicher, J.D. (John D.), Chami, N. (Nathalie), Kacprowski, T. (Tim), Nomura, A. (Akihiro), Chen, M.-H. (Ming-Huei), Yanek, L.R. (Lisa), Tajuddin, S.M. (Salman M.), Schick, U.M. (Ursula), Slater, A.J. (Andrew J.), Pankratz, V.S. (Shane), Polfus, L. (Linda), Schurmann, C. (Claudia), Giri, A. (Ayush), Brody, J.A. (Jennifer A.), Lange, L.A. (Leslie), Manichaikul, A. (Ani), Hill, W.D. (W. David), Pazoki, R. (Raha), Elliot, P. (Paul), Evangelou, E. (Evangelos), Tzoulaki, I., Gao, H. (He), Vergnaud, A.-C. (Anne-Claire), Mathias, J. (Jasmine), Becker, D.M. (Diane), Becker, L.C. (Lewis), Burt, A.D. (Alastair), Crosslin, D.R. (David), Lyytikäinen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Hernesniemi, J. (Jussi), Kähönen, M. (Mika), Raitoharju, E. (Emma), Mononen, K. (Kari), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Cushman, M. (Mary Ann), Zakai, N.A. (Neil), Nickerson, D.A. (Deborah), Raffield, L.M. (Laura M.), Quarells, R. (Rakale), Willer, C.J. (Cristen), Peloso, G.M. (Gina), Abecasis, G.R. (Gonçalo), Liu, D. (Dajiang), Deloukas, P. (Panagiotis), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Fornage, M. (Myriam), Richard, M. (Melissa), Tardif, J.-C. (Jean-Claude), Rioux, J.D. (John D.), Dube, M.-P. (Marie-Pierre), de Denus, S. (Simon), Lu, Y. (Yingchang), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Smith, A.V. (Albert Vernon), Harris, T.B. (Tamara), Launer, L.J. (Lenore J.), Gudnason, V. (Vilmundur), Velez Edwards, D.R. (Digna R.), Torstenson, E.S. (Eric S.), Liu, Y. (YongMei), Tracy, R.P. (Russell), Rotter, J.I. (Jerome I.), Rich, S.S. (Stephen), Highland, H. (Heather), Boerwinkle, E.A. (Eric), Li, J. (Jin), Lange, E.M. (Ethan), Wilson, J.F. (James), Mihailov, E. (Evelin), Mägi, R. (Reedik), Hirschhorn, J.N. (Joel), Metspalu, A. (Andres), Esko, T. (Tõnu), Vacchi-Suzzi, C. (Caterina), Nalls, M.A. (Michael), Zonderman, A.B., Evans, M.K. (Michele), Engström, G., Orho-Melander, M. (Marju), Melander, O. (Olle), O'Donoghue, M.L. (Michelle L.), Waterworth, D. (Dawn), Wallentin, L.C. (Lars), White, H.D. (Harvey D.), Floyd, J. (James), Bartz, T.M. (Traci M.), Rice, K.M. (Kenneth), Psaty, B.M. (Bruce), Starr, J.M. (John), Liewald, D.C.M. (David), Hayward, C. (Caroline), Deary, I.J. (Ian), Greinacher, A. (Andreas), Völker, U. (Uwe), Thiele, T. (Thomas), Völzke, H. (Henry), Rooij, F.J.A. (Frank) van, Uitterlinden, A.G. (André), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Kathiresan, S. (Sekar), Faraday, N. (Nauder), Auer, P. (Paul), Reiner, A. (Alexander), Lettre, G. (Guillaume), Johnson, A.D. (Andrew), Eicher, J.D. (John D.), Chami, N. (Nathalie), Kacprowski, T. (Tim), Nomura, A. (Akihiro), Chen, M.-H. (Ming-Huei), Yanek, L.R. (Lisa), Tajuddin, S.M. (Salman M.), Schick, U.M. (Ursula), Slater, A.J. (Andrew J.), Pankratz, V.S. (Shane), Polfus, L. (Linda), Schurmann, C. (Claudia), Giri, A. (Ayush), Brody, J.A. (Jennifer A.), Lange, L.A. (Leslie), Manichaikul, A. (Ani), Hill, W.D. (W. David), Pazoki, R. (Raha), Elliot, P. (Paul), Evangelou, E. (Evangelos), Tzoulaki, I., Gao, H. (He), Vergnaud, A.-C. (Anne-Claire), Mathias, J. (Jasmine), Becker, D.M. (Diane), Becker, L.C. (Lewis), Burt, A.D. (Alastair), Crosslin, D.R. (David), Lyytikäinen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Hernesniemi, J. (Jussi), Kähönen, M. (Mika), Raitoharju, E. (Emma), Mononen, K. (Kari), Raitakari, O.T. (Olli T.), Lehtimäki, T. (Terho), Cushman, M. (Mary Ann), Zakai, N.A. (Neil), Nickerson, D.A. (Deborah), Raffield, L.M. (Laura M.), Quarells, R. (Rakale), Willer, C.J. (Cristen), Peloso, G.M. (Gina), Abecasis, G.R. (Gonçalo), Liu, D. (Dajiang), Deloukas, P. (Panagiotis), Samani, N.J. (Nilesh), Schunkert, H. (Heribert), Erdmann, J. (Jeanette), Fornage, M. (Myriam), Richard, M. (Melissa), Tardif, J.-C. (Jean-Claude), Rioux, J.D. (John D.), Dube, M.-P. (Marie-Pierre), de Denus, S. (Simon), Lu, Y. (Yingchang), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Smith, A.V. (Albert Vernon), Harris, T.B. (Tamara), Launer, L.J. (Lenore J.), Gudnason, V. (Vilmundur), Velez Edwards, D.R. (Digna R.), Torstenson, E.S. (Eric S.), Liu, Y. (YongMei), Tracy, R.P. (Russell), Rotter, J.I. (Jerome I.), Rich, S.S. (Stephen), Highland, H. (Heather), Boerwinkle, E.A. (Eric), Li, J. (Jin), Lange, E.M. (Ethan), Wilson, J.F. (James), Mihailov, E. (Evelin), Mägi, R. (Reedik), Hirschhorn, J.N. (Joel), Metspalu, A. (Andres), Esko, T. (Tõnu), Vacchi-Suzzi, C. (Caterina), Nalls, M.A. (Michael), Zonderman, A.B., Evans, M.K. (Michele), Engström, G., Orho-Melander, M. (Marju), Melander, O. (Olle), O'Donoghue, M.L. (Michelle L.), Waterworth, D. (Dawn), Wallentin, L.C. (Lars), White, H.D. (Harvey D.), Floyd, J. (James), Bartz, T.M. (Traci M.), Rice, K.M. (Kenneth), Psaty, B.M. (Bruce), Starr, J.M. (John), Liewald, D.C.M. (David), Hayward, C. (Caroline), Deary, I.J. (Ian), Greinacher, A. (Andreas), Völker, U. (Uwe), Thiele, T. (Thomas), Völzke, H. (Henry), Rooij, F.J.A. (Frank) van, Uitterlinden, A.G. (André), Franco, O.H. (Oscar), Dehghan, A. (Abbas), Edwards, T.L. (Todd L.), Ganesh, S.K. (Santhi), Kathiresan, S. (Sekar), Faraday, N. (Nauder), Auer, P. (Paul), Reiner, A. (Alexander), Lettre, G. (Guillaume), and Johnson, A.D. (Andrew)
Abstract: Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets’ important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
Published: 2016
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9. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Author: Vries, P.S. (Paul) de, Chasman, D.I. (Daniel), Sabater-Lleal, M. (Maria), Chen, M.-H. (Ming-Huei), Huffman, J.E. (Jennifer E.), Steri, M. (Maristella), Tang, W. (Weihong), Teumer, A. (Alexander), Marioni, R.E. (Riccardo), Grossmann, V. (Vera), Hottenga, J.J. (Jouke Jan), Trompet, S. (Stella), Müller-Nurasyid, M. (Martina), Zhao, J.H. (Jing Hua), Brody, J.A. (Jennifer A.), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Wang, J.J. (Jie Jin), Auer, P. (Paul), Attia, J. (John), Yanek, L.R. (Lisa), Ahluwalia, T.S. (Tarunveer Singh), Lahti, J. (Jari), Venturini, C. (Cristina), Tanaka, T. (Toshiko), Bielak, L.F. (Lawrence F.), Joshi, P.K. (Peter), Rocanin-Arjo, A. (Ares), Kolcic, I. (Ivana), Navarro, P. (Pau), Rose, L.M. (Lynda), Oldmeadow, C. (Christopher), Riess, H. (Helene), Mazur, J. (Johanna), Basu, S. (Saonli), Goel, A. (Anuj), Yang, Q. (Qiong), Ghanbari, M. (Mohsen), Willemsen, G. (Gonneke), Rumley, A. (Ann), Fiorillo, E. (Edoardo), Craen, A.J. (Anton) de, Grotevendt, A. (Anne), Scott, R.A. (Robert), Taylor, K.D. (Kent D.), Delgado, G.E. (Graciela E.), Yao, J. (Jie), Kifley, A. (Annette), Kooperberg, C. (Charles), Qayyum, Q. (Rehan), Lopez, L. (Lornam), Berentzen, T.L. (Tina L.), Räikkönen, K. (Katri), Mangino, M. (Massimo), Bandinelli, S. (Stefania), Peyser, P.A. (Patricia A.), Wild, S. (Sarah), Tregouet, D.-A. (David-Alexandre), Wright, A.F. (Alan), Marten, J. (Jonathan), Zemunik, T. (Tatijana), Morrison, A.C. (Alanna), Sennblad, B. (Bengt), Tofler, G.H. (Geoffrey), Maat, M.P.M. (Moniek) de, Geus, E.J.C. (Eco) de, Lowe, G.D. (Gordon D.), Zoledziewska, M. (Magdalena), Sattar, N. (Naveed), Binder, H. (Harald), Völker, U. (Uwe), Waldenberger, M. (Melanie), Khaw, K.-T. (Kay-Tee), McKnight, B. (Barbara), Huang, J. (Jian), Jenny, N.S. (Nancy), Holliday, E.G. (Elizabeth), Qi, L. (Lihong), Mcevoy, M.G. (Mark G.), Becker, D.M. (Diane), Starr, J.M. (John), Sarin, A.-P., Hysi, P.G. (Pirro), Hernandez, D.G. (Dena), Jhun, M.A. (Min A.), Campbell, H. (Harry), Hamsten, A. (Anders), Sarin, F. (Fernando), McArdle, W.L. (Wendy), Slagboom, P.E. (Eline), Zeller, T. (Tanja), Koenig, W. (Wolfgang), Psaty, B. (Brucem), Haritunians, T. (Talin), Liu, J. (Jingmin), Palotie, A. (Aarno), Uitterlinden, A.G. (André), Stott, D.J. (David J.), Hofman, A. (Albert), Franco, O.H. (Oscar), Polasek, O. (Ozren), Rudan, I. (Igor), Morange, P.-E. (P.), Wilson, J.F. (James F.), Kardia, S.L. (Sharon L.r), Ferrucci, L. (Luigi), Spector, T.D. (Timothy), Eriksson, J.G. (Johan G.), Hansen, T. (Torben), Deary, I.J. (Ian), Becker, L.C. (Lewis), Scott, R.J. (Rodney), Mitchell, P. (Paul), März, W. (Winfried), Wareham, N.J. (Nick J.), Peters, A. (Annette), Greinacher, A. (Andreas), Wild, P.S. (Philipp S.), Jukema, J.W. (Jan Wouter), Boomsma, D.I. (Dorret), Hayward, C. (Caroline), Cucca, F. (Francesco), Tracy, R.P. (Russell), Watkins, H. (Hugh), Reiner, A.P. (Alex P.), Folsom, A.R. (Aaron), Ridker, P.M. (Paul), O'Donnell, C.J. (Christopher J.), Smith, N.L. (Nicholas L.), Strachan, D.P. (David P.), Dehghan, A. (Abbas), Vries, P.S. (Paul) de, Chasman, D.I. (Daniel), Sabater-Lleal, M. (Maria), Chen, M.-H. (Ming-Huei), Huffman, J.E. (Jennifer E.), Steri, M. (Maristella), Tang, W. (Weihong), Teumer, A. (Alexander), Marioni, R.E. (Riccardo), Grossmann, V. (Vera), Hottenga, J.J. (Jouke Jan), Trompet, S. (Stella), Müller-Nurasyid, M. (Martina), Zhao, J.H. (Jing Hua), Brody, J.A. (Jennifer A.), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Wang, J.J. (Jie Jin), Auer, P. (Paul), Attia, J. (John), Yanek, L.R. (Lisa), Ahluwalia, T.S. (Tarunveer Singh), Lahti, J. (Jari), Venturini, C. (Cristina), Tanaka, T. (Toshiko), Bielak, L.F. (Lawrence F.), Joshi, P.K. (Peter), Rocanin-Arjo, A. (Ares), Kolcic, I. (Ivana), Navarro, P. (Pau), Rose, L.M. (Lynda), Oldmeadow, C. (Christopher), Riess, H. (Helene), Mazur, J. (Johanna), Basu, S. (Saonli), Goel, A. (Anuj), Yang, Q. (Qiong), Ghanbari, M. (Mohsen), Willemsen, G. (Gonneke), Rumley, A. (Ann), Fiorillo, E. (Edoardo), Craen, A.J. (Anton) de, Grotevendt, A. (Anne), Scott, R.A. (Robert), Taylor, K.D. (Kent D.), Delgado, G.E. (Graciela E.), Yao, J. (Jie), Kifley, A. (Annette), Kooperberg, C. (Charles), Qayyum, Q. (Rehan), Lopez, L. (Lornam), Berentzen, T.L. (Tina L.), Räikkönen, K. (Katri), Mangino, M. (Massimo), Bandinelli, S. (Stefania), Peyser, P.A. (Patricia A.), Wild, S. (Sarah), Tregouet, D.-A. (David-Alexandre), Wright, A.F. (Alan), Marten, J. (Jonathan), Zemunik, T. (Tatijana), Morrison, A.C. (Alanna), Sennblad, B. (Bengt), Tofler, G.H. (Geoffrey), Maat, M.P.M. (Moniek) de, Geus, E.J.C. (Eco) de, Lowe, G.D. (Gordon D.), Zoledziewska, M. (Magdalena), Sattar, N. (Naveed), Binder, H. (Harald), Völker, U. (Uwe), Waldenberger, M. (Melanie), Khaw, K.-T. (Kay-Tee), McKnight, B. (Barbara), Huang, J. (Jian), Jenny, N.S. (Nancy), Holliday, E.G. (Elizabeth), Qi, L. (Lihong), Mcevoy, M.G. (Mark G.), Becker, D.M. (Diane), Starr, J.M. (John), Sarin, A.-P., Hysi, P.G. (Pirro), Hernandez, D.G. (Dena), Jhun, M.A. (Min A.), Campbell, H. (Harry), Hamsten, A. (Anders), Sarin, F. (Fernando), McArdle, W.L. (Wendy), Slagboom, P.E. (Eline), Zeller, T. (Tanja), Koenig, W. (Wolfgang), Psaty, B. (Brucem), Haritunians, T. (Talin), Liu, J. (Jingmin), Palotie, A. (Aarno), Uitterlinden, A.G. (André), Stott, D.J. (David J.), Hofman, A. (Albert), Franco, O.H. (Oscar), Polasek, O. (Ozren), Rudan, I. (Igor), Morange, P.-E. (P.), Wilson, J.F. (James F.), Kardia, S.L. (Sharon L.r), Ferrucci, L. (Luigi), Spector, T.D. (Timothy), Eriksson, J.G. (Johan G.), Hansen, T. (Torben), Deary, I.J. (Ian), Becker, L.C. (Lewis), Scott, R.J. (Rodney), Mitchell, P. (Paul), März, W. (Winfried), Wareham, N.J. (Nick J.), Peters, A. (Annette), Greinacher, A. (Andreas), Wild, P.S. (Philipp S.), Jukema, J.W. (Jan Wouter), Boomsma, D.I. (Dorret), Hayward, C. (Caroline), Cucca, F. (Francesco), Tracy, R.P. (Russell), Watkins, H. (Hugh), Reiner, A.P. (Alex P.), Folsom, A.R. (Aaron), Ridker, P.M. (Paul), O'Donnell, C.J. (Christopher J.), Smith, N.L. (Nicholas L.), Strachan, D.P. (David P.), and Dehghan, A. (Abbas)
Abstract: Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels.We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ~120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.
Published: 2016
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10. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Author: Zheng, H.-F. (Hou-Feng), Forgetta, V. (Vincenzo), Hsu, Y.-H. (Yi-Hsiang), Estrada Gil, K. (Karol), Rosello-Diez, A. (Alberto), Leo, P.J. (Paul), Dahia, C.L. (Chitra L.), Park-Min, K.H. (Kyung Hyun), Tobias, J.H. (Jon), Kooperberg, C. (Charles), Kleinman, A. (Aaron), Styrkarsdottir, U. (Unnur), Liu, C.-T. (Ching-Ti), Uggla, C. (Charlotta), Evans, D.S. (Daniel), Nielson, C. (Carrie), Walter, K. (Klaudia), Pettersson-Kymmer, U. (Ulrika), McCarthy, S. (Shane), Eriksson, J. (Joel), Kwan, T. (Tony), Jhamai, M. (Mila), Trajanoska, K. (Katerina), Memari, Y. (Yasin), Min, J.L. (Josine L.), Huang, J. (Jie), Danecek, P. (Petr), Wilmot, B. (Beth), Li, R. (Rui), Chou, W.-C. (Wen-Chi), Mokry, L.E. (Lauren E.), Moayyeri, A. (Alireza), Claussnitzer, M. (Melina), Cheng, C.-H. (Chia-Ho), Cheung, W. (Warren), Medina-Gomez, M.C. (Carolina), Ge, B. (Bing), Chen, S.-H. (Shu-Huang), Choi, K. (Kunho), Oei, L. (Ling), Fraser, J. (James), Kraaij, R. (Robert), Hibbs, M.A. (Matthew A.), Gregson, C.L. (Celia L.), Paquette, D. (Denis), Hofman, A. (Albert), Wibom, C. (Carl), Tranah, G.J. (Gregory), Marshall, M. (Mhairi), Gardiner, B.B. (Brooke B.), Cremin, K. (Katie), Auer, P. (Paul), Hsu, L. (Li), Ring, S. (Susan), Tung, J.Y. (Joyce Y.), Thorleifsson, G. (Gudmar), Enneman, A.W. (Anke), Schoor, N.M. (Natasja) van, Groot, L.C.P.G.M. (Lisette) de, Velde, N. (Nathalie) van der, Melin, B. (Beatrice), Kemp, J.P. (John), Christiansen, C., Sayers, I. (Ian), Zhou, Y. (Yanhua), Calderari, S. (Sophie), Rooij, J.G.J. (Jeroen) van, Carlson, C. (Chris), Peters, U. (Ulrike), Berlivet, S. (Soizik), Dostie, J. (Josée), Uitterlinden, A.G. (André), Williams, S.R. (Stephen R.), Farber, C. (Charles), Grinberg, D. (Daniel), LaCroix, A.Z. (Andrea), Haessler, J. (Jeff), Chasman, D.I. (Daniel), Giulianini, F. (Franco), Rose, L.M. (Lynda M.), Ridker, P.M. (Paul), Eisman, J.A. (John), Nguyen, T.V. (Tuan), Center, J.R. (Jacqueline), Nogues, X. (Xavier), Garcia-Giralt, N. (Natàlia), Launer, L.J. (Lenore), Gudnason, V. (Vilmunder), Mellström, D. (Dan), Vandenput, L. (Liesbeth), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Karlsson, M. (Magnus), Ljunggren, O. (Östen), Svensson, O. (Olle), Hallmans, G. (Göran), Rousseau, M.F. (Francois), Giroux, S. (Sylvie), Bussière, J. (Johanne), Arp, P.P. (Pascal), Koromani, F. (Fjorda), Prince, R.L. (Richard L.), Lewis, J.R. (Joshua), Langdahl, B.L. (Bente), Hermann, A.P. (A. Pernille), Jensen, J.-E.B. (Jens-Erik B.), Kaptoge, S. (Stephen), Khaw, K.T., Reeve, J. (Jonathan), Formosa, M.M. (Melissa M.), Xuereb-Anastasi, A. (Angela), Åkesson, K. (Kristina), McGuigan, F.E., Garg, G. (Gaurav), Olmos, D. (David), Zarrabeitia, M.T. (María), Riancho, J.A. (José), Ralston, S.H. (Stuart), Alonso, N. (Nerea), Jiang, X. (Xi), Goltzman, D. (David), Pastinen, T. (Tomi), Grundberg, E. (Elin), Gauguier, D. (Dominique), Orwoll, E.S. (Eric), Karasik, D. (David), Smith, A.V. (Davey), Siggeirsdottir, K. (Kristin), Harris, T.B. (Tamara), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Thorsteinsdottir, U. (Unnur), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Soranzo, N. (Nicole), Durbin, R. (Richard), Wilson, S.G. (Scott), Ntzani, E.E. (Evangelia), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Hinds, D.A. (David A.), Spector, T.D. (Timothy), Cupples, L.A. (Adrienne), Ohlsson, C. (Claes), Greenwood, C.M.T. (Celia), Jackson, R.D. (Rebecca), Rowe, D.W. (David W.), Loomis, C.A. (Cynthia A.), Evans, D.M. (David M.), Ackert-Bicknell, C.L. (Cheryl), Joyner, A.L. (Alexandra L.), Duncan, E.L. (Emma), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), Richards, J.B. (Brent), Zheng, H.-F. (Hou-Feng), Forgetta, V. (Vincenzo), Hsu, Y.-H. (Yi-Hsiang), Estrada Gil, K. (Karol), Rosello-Diez, A. (Alberto), Leo, P.J. (Paul), Dahia, C.L. (Chitra L.), Park-Min, K.H. (Kyung Hyun), Tobias, J.H. (Jon), Kooperberg, C. (Charles), Kleinman, A. (Aaron), Styrkarsdottir, U. (Unnur), Liu, C.-T. (Ching-Ti), Uggla, C. (Charlotta), Evans, D.S. (Daniel), Nielson, C. (Carrie), Walter, K. (Klaudia), Pettersson-Kymmer, U. (Ulrika), McCarthy, S. (Shane), Eriksson, J. (Joel), Kwan, T. (Tony), Jhamai, M. (Mila), Trajanoska, K. (Katerina), Memari, Y. (Yasin), Min, J.L. (Josine L.), Huang, J. (Jie), Danecek, P. (Petr), Wilmot, B. (Beth), Li, R. (Rui), Chou, W.-C. (Wen-Chi), Mokry, L.E. (Lauren E.), Moayyeri, A. (Alireza), Claussnitzer, M. (Melina), Cheng, C.-H. (Chia-Ho), Cheung, W. (Warren), Medina-Gomez, M.C. (Carolina), Ge, B. (Bing), Chen, S.-H. (Shu-Huang), Choi, K. (Kunho), Oei, L. (Ling), Fraser, J. (James), Kraaij, R. (Robert), Hibbs, M.A. (Matthew A.), Gregson, C.L. (Celia L.), Paquette, D. (Denis), Hofman, A. (Albert), Wibom, C. (Carl), Tranah, G.J. (Gregory), Marshall, M. (Mhairi), Gardiner, B.B. (Brooke B.), Cremin, K. (Katie), Auer, P. (Paul), Hsu, L. (Li), Ring, S. (Susan), Tung, J.Y. (Joyce Y.), Thorleifsson, G. (Gudmar), Enneman, A.W. (Anke), Schoor, N.M. (Natasja) van, Groot, L.C.P.G.M. (Lisette) de, Velde, N. (Nathalie) van der, Melin, B. (Beatrice), Kemp, J.P. (John), Christiansen, C., Sayers, I. (Ian), Zhou, Y. (Yanhua), Calderari, S. (Sophie), Rooij, J.G.J. (Jeroen) van, Carlson, C. (Chris), Peters, U. (Ulrike), Berlivet, S. (Soizik), Dostie, J. (Josée), Uitterlinden, A.G. (André), Williams, S.R. (Stephen R.), Farber, C. (Charles), Grinberg, D. (Daniel), LaCroix, A.Z. (Andrea), Haessler, J. (Jeff), Chasman, D.I. (Daniel), Giulianini, F. (Franco), Rose, L.M. (Lynda M.), Ridker, P.M. (Paul), Eisman, J.A. (John), Nguyen, T.V. (Tuan), Center, J.R. (Jacqueline), Nogues, X. (Xavier), Garcia-Giralt, N. (Natàlia), Launer, L.J. (Lenore), Gudnason, V. (Vilmunder), Mellström, D. (Dan), Vandenput, L. (Liesbeth), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Karlsson, M. (Magnus), Ljunggren, O. (Östen), Svensson, O. (Olle), Hallmans, G. (Göran), Rousseau, M.F. (Francois), Giroux, S. (Sylvie), Bussière, J. (Johanne), Arp, P.P. (Pascal), Koromani, F. (Fjorda), Prince, R.L. (Richard L.), Lewis, J.R. (Joshua), Langdahl, B.L. (Bente), Hermann, A.P. (A. Pernille), Jensen, J.-E.B. (Jens-Erik B.), Kaptoge, S. (Stephen), Khaw, K.T., Reeve, J. (Jonathan), Formosa, M.M. (Melissa M.), Xuereb-Anastasi, A. (Angela), Åkesson, K. (Kristina), McGuigan, F.E., Garg, G. (Gaurav), Olmos, D. (David), Zarrabeitia, M.T. (María), Riancho, J.A. (José), Ralston, S.H. (Stuart), Alonso, N. (Nerea), Jiang, X. (Xi), Goltzman, D. (David), Pastinen, T. (Tomi), Grundberg, E. (Elin), Gauguier, D. (Dominique), Orwoll, E.S. (Eric), Karasik, D. (David), Smith, A.V. (Davey), Siggeirsdottir, K. (Kristin), Harris, T.B. (Tamara), Zillikens, M.C. (Carola), Meurs, J.B.J. (Joyce) van, Thorsteinsdottir, U. (Unnur), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Soranzo, N. (Nicole), Durbin, R. (Richard), Wilson, S.G. (Scott), Ntzani, E.E. (Evangelia), Brown, M.A. (Matthew), Zwart, J-A. (John-Anker), Hinds, D.A. (David A.), Spector, T.D. (Timothy), Cupples, L.A. (Adrienne), Ohlsson, C. (Claes), Greenwood, C.M.T. (Celia), Jackson, R.D. (Rebecca), Rowe, D.W. (David W.), Loomis, C.A. (Cynthia A.), Evans, D.M. (David M.), Ackert-Bicknell, C.L. (Cheryl), Joyner, A.L. (Alexandra L.), Duncan, E.L. (Emma), Kiel, D.P. (Douglas P.), Rivadeneira Ramirez, F. (Fernando), and Richards, J.B. (Brent)
Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10-14), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10-11; ncases = 98,742 and n controls = 409,511). Using an En1 cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10-11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation
Published: 2015
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11. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

Author: Huffman, J.E. (Jennifer), Vries, P.S. (Paul) de, Morrison, A.C. (Alanna), Sabater-Lleal, M. (Maria), Kacprowski, T. (Tim), Auer, P. (Paul), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel), Chen, M.-H. (Ming-Huei), Guo, X. (Xiuqing), Lin, L.-A. (Li-An), Marioni, R.E. (Riccardo), Müller-Nurasyid, M. (Martina), Yanek, L.R. (Lisa), Pankratz, V.S. (Shane), Grove, M.L. (Megan L.), Maat, M.P.M. (Moniek) de, Cushman, M. (Mary Ann), Wiggins, K.L. (Kerri), Qi, L. (Lihong), Sennblad, B. (Bengt), Harris, S.E. (Sarah), Polasek, O. (Ozren), Riess, H. (Helene), Rivadeneira Ramirez, F. (Fernando), Rose, L.M. (Lynda), Goel, A. (Anuj), Taylor, K.D. (Kent D.), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Yao, J. (Jiefen), Tang, W. (Weihong), Levy, D. (Daniel), Waldenberger, M. (Melanie), Becker, D.M. (Diane), Folsom, A.R. (Aaron), Giulianini, F. (Franco), Greinacher, A. (Andreas), Hofman, A. (Albert), Huang, C.-C. (Chiang-Ching), Kooperberg, C. (Charles), Silveira, A. (Angela), Starr, J.M. (John), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Wright, A. (Alan), McKnight, B. (Barbara), Franco, O.H. (Oscar), Zakai, N.A. (Neil), Mathias, J. (Jasmine), Psaty, B.M. (Bruce), Ridker, P.M. (Paul), Tofler, G.H. (Geoffrey), Völker, U. (Uwe), Watkins, H. (Hugh), Fornage, M. (Myriam), Hamsten, A. (Anders), Deary, I.J. (Ian), Boerwinkle, E.A. (Eric), Koenig, W. (Wolfgang), Rotter, J.I. (Jerome I.), Hayward, C. (Caroline), Dehghan, A. (Abbas), Reiner, A. (Alexander), O'Donnell, C.J. (Christopher), Smith, N.L. (Nicholas), Huffman, J.E. (Jennifer), Vries, P.S. (Paul) de, Morrison, A.C. (Alanna), Sabater-Lleal, M. (Maria), Kacprowski, T. (Tim), Auer, P. (Paul), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel), Chen, M.-H. (Ming-Huei), Guo, X. (Xiuqing), Lin, L.-A. (Li-An), Marioni, R.E. (Riccardo), Müller-Nurasyid, M. (Martina), Yanek, L.R. (Lisa), Pankratz, V.S. (Shane), Grove, M.L. (Megan L.), Maat, M.P.M. (Moniek) de, Cushman, M. (Mary Ann), Wiggins, K.L. (Kerri), Qi, L. (Lihong), Sennblad, B. (Bengt), Harris, S.E. (Sarah), Polasek, O. (Ozren), Riess, H. (Helene), Rivadeneira Ramirez, F. (Fernando), Rose, L.M. (Lynda), Goel, A. (Anuj), Taylor, K.D. (Kent D.), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Yao, J. (Jiefen), Tang, W. (Weihong), Levy, D. (Daniel), Waldenberger, M. (Melanie), Becker, D.M. (Diane), Folsom, A.R. (Aaron), Giulianini, F. (Franco), Greinacher, A. (Andreas), Hofman, A. (Albert), Huang, C.-C. (Chiang-Ching), Kooperberg, C. (Charles), Silveira, A. (Angela), Starr, J.M. (John), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Wright, A. (Alan), McKnight, B. (Barbara), Franco, O.H. (Oscar), Zakai, N.A. (Neil), Mathias, J. (Jasmine), Psaty, B.M. (Bruce), Ridker, P.M. (Paul), Tofler, G.H. (Geoffrey), Völker, U. (Uwe), Watkins, H. (Hugh), Fornage, M. (Myriam), Hamsten, A. (Anders), Deary, I.J. (Ian), Boerwinkle, E.A. (Eric), Koenig, W. (Wolfgang), Rotter, J.I. (Jerome I.), Hayward, C. (Caroline), Dehghan, A. (Abbas), Reiner, A. (Alexander), O'Donnell, C.J. (Christopher), and Smith, N.L. (Nicholas)
Abstract: Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified
Published: 2015
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12. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

Author: Lange, L.A. (Leslie), Hu, Y. (Youna), Zhang, H. (He), Xue, C. (Chenyi), Schmidt, E.M. (Ellen), Tang, Z.-Z. (Zheng-Zheng), Bizon, C. (Chris), Lange, E.M. (Ethan), Smith, A.V. (Davey), Turner, E.H. (Emily), Jun, Y. (Yang), Kang, H.M. (Hyun Min), Peloso, G.M. (Gina), Auer, P. (Paul), Li, K.-P. (Kuo-Ping), Flannick, J. (Jason), Zhang, J. (Ji), Fuchsberger, C. (Christian), Gaulton, K. (Kyle), Lindgren, C.M. (Cecilia), Locke, A. (Adam), Manning, A.K. (Alisa), Sim, X. (Xueling), Rivas, M.A. (Manuel), Holmen, O.L. (Oddgeir), Gottesman, R.F. (Rebecca), Lu, Y. (Yingchang), Ruderfer, D. (Douglas), Stahl, E.A. (Eli), Duan, Q. (Qing), Li, Y. (Yun), Durda, P. (Peter), Jiao, S. (Shuo), Isaacs, A.J. (Aaron), Hofman, A. (Albert), Bis, J.C. (Joshua), Correa, D.D., Griswold, M.D. (Michael), Jakobsdottir, M. (Margret), Schreiner, P.J. (Pamela), Feitosa, M.F. (Mary Furlan), Zhang, Q. (Qunyuan), Huffman, J.E. (Jennifer), Crosby, S., Wassel, C.L. (Christina), Do, R. (Ron), Franceschini, N. (Nora), Martin, L.W. (Lisa), Robinson, J.G. (Jennifer), Assimes, T.L. (Themistocles), Crosslin, D.R. (David), Rosenthal, E.A. (Elisabeth), Tsai, M.Y. (Michael), Rieder, M. (Mark), Farlow, D.N. (Deborah), Folsom, A.R. (Aaron), Lumley, T. (Thomas), Fox, E.R. (Ervin), Carlson, C.S. (Christopher), Peters, U. (Ulrike), Jackson, R.D. (Rebecca), Duijn, C.M. (Cornelia) van, Uitterlinden, A.G. (André), Levy, D. (Daniel), Rotter, J.I. (Jerome), Taylor, H.A. (Herman), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Fornage, M. (Myriam), Borecki, I.B. (Ingrid), Hayward, C. (Caroline), Rudan, I. (Igor), Chen, Y.E. (Y. Eugene), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Sætrom, P. (Pål), Hveem, K. (Kristian), Boehnke, M. (Michael), Groop, L. (Leif), McCarthy, M.I. (Mark), Meitinger, T. (Thomas), Ballantyne, C. (Christie), Gabriel, S.B. (Stacey), O'Donnell, C.J. (Christopher), Post, W.S. (Wendy S.), North, K.E. (Kari), Reiner, A. (Alexander), Boerwinkle, E.A. (Eric), Psaty, B.M. (Bruce), Altshuler, D. (David), Kathiresan, S. (Sekar), Lin, D.Y. (Dan), Jarvik, G.P. (Gail), Cupples, L.A. (Adrienne), Kooperberg, C. (Charles), Wilson, J.G. (James), Nickerson, D.A. (Deborah), Abecasis, G.R. (Gonçalo), Rich, S.S. (Stephen), Tracy, R.P. (Russell), Willer, C.J. (Cristen), Lange, L.A. (Leslie), Hu, Y. (Youna), Zhang, H. (He), Xue, C. (Chenyi), Schmidt, E.M. (Ellen), Tang, Z.-Z. (Zheng-Zheng), Bizon, C. (Chris), Lange, E.M. (Ethan), Smith, A.V. (Davey), Turner, E.H. (Emily), Jun, Y. (Yang), Kang, H.M. (Hyun Min), Peloso, G.M. (Gina), Auer, P. (Paul), Li, K.-P. (Kuo-Ping), Flannick, J. (Jason), Zhang, J. (Ji), Fuchsberger, C. (Christian), Gaulton, K. (Kyle), Lindgren, C.M. (Cecilia), Locke, A. (Adam), Manning, A.K. (Alisa), Sim, X. (Xueling), Rivas, M.A. (Manuel), Holmen, O.L. (Oddgeir), Gottesman, R.F. (Rebecca), Lu, Y. (Yingchang), Ruderfer, D. (Douglas), Stahl, E.A. (Eli), Duan, Q. (Qing), Li, Y. (Yun), Durda, P. (Peter), Jiao, S. (Shuo), Isaacs, A.J. (Aaron), Hofman, A. (Albert), Bis, J.C. (Joshua), Correa, D.D., Griswold, M.D. (Michael), Jakobsdottir, M. (Margret), Schreiner, P.J. (Pamela), Feitosa, M.F. (Mary Furlan), Zhang, Q. (Qunyuan), Huffman, J.E. (Jennifer), Crosby, S., Wassel, C.L. (Christina), Do, R. (Ron), Franceschini, N. (Nora), Martin, L.W. (Lisa), Robinson, J.G. (Jennifer), Assimes, T.L. (Themistocles), Crosslin, D.R. (David), Rosenthal, E.A. (Elisabeth), Tsai, M.Y. (Michael), Rieder, M. (Mark), Farlow, D.N. (Deborah), Folsom, A.R. (Aaron), Lumley, T. (Thomas), Fox, E.R. (Ervin), Carlson, C.S. (Christopher), Peters, U. (Ulrike), Jackson, R.D. (Rebecca), Duijn, C.M. (Cornelia) van, Uitterlinden, A.G. (André), Levy, D. (Daniel), Rotter, J.I. (Jerome), Taylor, H.A. (Herman), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Fornage, M. (Myriam), Borecki, I.B. (Ingrid), Hayward, C. (Caroline), Rudan, I. (Igor), Chen, Y.E. (Y. Eugene), Bottinger, E.P. (Erwin), Loos, R.J.F. (Ruth), Sætrom, P. (Pål), Hveem, K. (Kristian), Boehnke, M. (Michael), Groop, L. (Leif), McCarthy, M.I. (Mark), Meitinger, T. (Thomas), Ballantyne, C. (Christie), Gabriel, S.B. (Stacey), O'Donnell, C.J. (Christopher), Post, W.S. (Wendy S.), North, K.E. (Kari), Reiner, A. (Alexander), Boerwinkle, E.A. (Eric), Psaty, B.M. (Bruce), Altshuler, D. (David), Kathiresan, S. (Sekar), Lin, D.Y. (Dan), Jarvik, G.P. (Gail), Cupples, L.A. (Adrienne), Kooperberg, C. (Charles), Wilson, J.G. (James), Nickerson, D.A. (Deborah), Abecasis, G.R. (Gonçalo), Rich, S.S. (Stephen), Tracy, R.P. (Russell), and Willer, C.J. (Cristen)
Abstract: Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previousl
Published: 2014
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13. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks

Author: Peloso, G.M. (Gina), Auer, P. (Paul), Bis, J.C. (Joshua), Voorman, J.M. (Jeanine), Morrison, A.C. (Alanna), Stitziel, N.O. (Nathan), Brody, J.A. (Jennifer A.), Khetarpal, S.A. (Sumeet), Crosby, S., Fornage, M. (Myriam), Isaacs, A.J. (Aaron), Jakobsdottir, M. (Margret), Feitosa, M.F. (Mary Furlan), Davies, G. (Gail), Huffman, J.E. (Jennifer), Manichaikul, A. (Ani), Davis, B. (Brian), Lohman, K. (Kurt), Joon, A.Y. (Aron), Smith, A.V. (Davey), Grove, M.L. (Megan), Zanoni, P. (Paolo), Redon, V. (Valeska), Demissie, S. (Serkalem), Lawson, K. (Kim), Peters, U. (Ulrike), Carlson, C.S. (Christopher), Jackson, R.D. (Rebecca), Ryckman, K.K. (Kelli), MacKey, R.H. (Rachel), Robinson, J.G. (Jennifer), Siscovick, D.S. (David), Schreiner, P.J. (Pamela), Mychaleckyj, J.C. (Josyf), Pankow, J.S. (James), Hofman, A. (Albert), Uitterlinden, A.G. (André), Harris, T.B. (Tamara), Taylor, K.D. (Kent), Stafford, M., Reynolds, L.M. (Lindsay), Marioni, R.E. (Riccardo), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Patel, A.P. (Aniruddh), Lu, Y. (Yingchang), Hindy, G. (George), Gottesman, R.F. (Rebecca), Bottinger, E.P. (Erwin), Melander, O. (Olle), Orho-Melander, M. (Marju), Loos, R.J.F. (Ruth), Duga, S. (Stefano), Merlini, P.A. (Piera), Farrall, M. (Martin), Goel, A. (Anuj), Asselta, R. (Rosanna), Girelli, D. (Domenico), Martinelli, N. (Nicola), Shah, S.H. (Svati), Kraus, T. (Thomas), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), McPherson, R. (Ruth), Watkins, H. (Hugh), Ardissino, D. (Diego), Zhang, Q. (Qunyuan), Wang, J. (Judy), Tsai, M.Y. (Michael), Taylor, H.A. (Herman), Correa, D.D., Griswold, M.D. (Michael), Lange, L.A. (Leslie), Starr, J.M. (John), Rudan, I. (Igor), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Ordovas, J.M. (Jose), Levy, D. (Daniel), Chen, Y.-D.I. (Y.-D. Ida), Reiner, A. (Alexander), Hayward, C. (Caroline), Polasek, O. (Ozren), Deary, I.J. (Ian), Borecki, I.B. (Ingrid), Liu, Y. (YongMei), Gudnason, V. (Vilmundur), Wilson, J.G. (James), Duijn, C.M. (Cornelia) van, Kooperberg, C. (Charles), Rich, S.S. (Stephen), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), O'Donnell, C.J. (Christopher), Rice, K.M. (Kenneth), Boerwinkle, E.A. (Eric), Kathiresan, S. (Sekar), Cupples, L.A. (Adrienne), Li, M. (Mingyao), Peloso, G.M. (Gina), Auer, P. (Paul), Bis, J.C. (Joshua), Voorman, J.M. (Jeanine), Morrison, A.C. (Alanna), Stitziel, N.O. (Nathan), Brody, J.A. (Jennifer A.), Khetarpal, S.A. (Sumeet), Crosby, S., Fornage, M. (Myriam), Isaacs, A.J. (Aaron), Jakobsdottir, M. (Margret), Feitosa, M.F. (Mary Furlan), Davies, G. (Gail), Huffman, J.E. (Jennifer), Manichaikul, A. (Ani), Davis, B. (Brian), Lohman, K. (Kurt), Joon, A.Y. (Aron), Smith, A.V. (Davey), Grove, M.L. (Megan), Zanoni, P. (Paolo), Redon, V. (Valeska), Demissie, S. (Serkalem), Lawson, K. (Kim), Peters, U. (Ulrike), Carlson, C.S. (Christopher), Jackson, R.D. (Rebecca), Ryckman, K.K. (Kelli), MacKey, R.H. (Rachel), Robinson, J.G. (Jennifer), Siscovick, D.S. (David), Schreiner, P.J. (Pamela), Mychaleckyj, J.C. (Josyf), Pankow, J.S. (James), Hofman, A. (Albert), Uitterlinden, A.G. (André), Harris, T.B. (Tamara), Taylor, K.D. (Kent), Stafford, M., Reynolds, L.M. (Lindsay), Marioni, R.E. (Riccardo), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Patel, A.P. (Aniruddh), Lu, Y. (Yingchang), Hindy, G. (George), Gottesman, R.F. (Rebecca), Bottinger, E.P. (Erwin), Melander, O. (Olle), Orho-Melander, M. (Marju), Loos, R.J.F. (Ruth), Duga, S. (Stefano), Merlini, P.A. (Piera), Farrall, M. (Martin), Goel, A. (Anuj), Asselta, R. (Rosanna), Girelli, D. (Domenico), Martinelli, N. (Nicola), Shah, S.H. (Svati), Kraus, T. (Thomas), Rader, D.J. (Daniel), Reilly, M.P. (Muredach), McPherson, R. (Ruth), Watkins, H. (Hugh), Ardissino, D. (Diego), Zhang, Q. (Qunyuan), Wang, J. (Judy), Tsai, M.Y. (Michael), Taylor, H.A. (Herman), Correa, D.D., Griswold, M.D. (Michael), Lange, L.A. (Leslie), Starr, J.M. (John), Rudan, I. (Igor), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Ordovas, J.M. (Jose), Levy, D. (Daniel), Chen, Y.-D.I. (Y.-D. Ida), Reiner, A. (Alexander), Hayward, C. (Caroline), Polasek, O. (Ozren), Deary, I.J. (Ian), Borecki, I.B. (Ingrid), Liu, Y. (YongMei), Gudnason, V. (Vilmundur), Wilson, J.G. (James), Duijn, C.M. (Cornelia) van, Kooperberg, C. (Charles), Rich, S.S. (Stephen), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), O'Donnell, C.J. (Christopher), Rice, K.M. (Kenneth), Boerwinkle, E.A. (Eric), Kathiresan, S. (Sekar), Cupples, L.A. (Adrienne), and Li, M. (Mingyao)
Abstract: Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121-], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
Published: 2014
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13 results on '"Auer, P. (Paul)"'

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

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

3. Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits

4. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

5. Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis

6. Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

7. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

8. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

9. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

10. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

11. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

12. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

13. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks

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