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1. A meta-analysis of genome-wide association studies identifies multiple longevity genes.

Author

Deelen, Joris, Evans, Daniel S, Arking, Dan E, Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K, Biggs, Mary L, van der Spek, Ashley, Atzmon, Gil, Ware, Erin B, Sarnowski, Chloé, Smith, Albert V, Seppälä, Ilkka, Cordell, Heather J, Dose, Janina, Amin, Najaf, Arnold, Alice M, Ayers, Kristin L, Barzilai, Nir, Becker, Elizabeth J, Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C, Cubaynes, Sarah, Cummings, Steven R, Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D, Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B, Huisman, Martijn, Hurme, Mikko A, Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon LR, Kingston, Andrew, Kirkwood, Thomas BL, Launer, Lenore J, Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B, Nie, Chao, Nohr, Ellen A, Orwoll, Eric S, Perls, Thomas T, Province, Michael A, Psaty, Bruce M, Raitakari, Olli T, Reinders, Marcel JT, Robine, Jean-Marie, Rotter, Jerome I, Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild IA, Taylor, Kent D, Uitterlinden, André G, van der Flier, Wiesje, van der Lee, Sven J, van Duijn, Cornelia M, van Heemst, Diana, Vaupel, James W, Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P, Lunetta, Kathryn L, Slagboom, P Eline, and Murabito, Joanne M

Subjects
Humans, Heat-Shock Proteins, Longevity, Apolipoprotein E2, Apolipoprotein E4, Genome-Wide Association Study
Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Published
2019

2. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author

Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, and Christiansen, Lene

Subjects
Biological Sciences, Genetics, Brain Disorders, Mental Health, Human Genome, Biotechnology, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Adolescent, Brain, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intelligence, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

Published
2018

5. Gene–Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

Author

Reynolds, Chandra A, Gatz, Margaret, Christensen, Kaare, Christiansen, Lene, Dahl Aslan, Anna K, Kaprio, Jaakko, Korhonen, Tellervo, Kremen, William S, Krueger, Robert, McGue, Matt, Neiderhiser, Jenae M, Pedersen, Nancy L, and for the IGEMS consortium

Subjects
Biological Psychology, Health Sciences, Psychology, Clinical Research, Behavioral and Social Science, Aging, Mental Health, Mental Illness, Basic Behavioral and Social Science, Brain Disorders, Depression, Genetics, Mind and Body, Neurosciences, 2.1 Biological and endogenous factors, 2.4 Surveillance and distribution, Adult, Aged, Aged, 80 and over, Apolipoproteins E, Body Mass Index, Cognition, Cognition Disorders, Environment, Female, Gene-Environment Interaction, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Risk Factors, Twins, Monozygotic, Gene-environment interaction, Twins, BMI, Cognitive performance, APOE, Variability gene, Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium, Gene–environment interaction, Zoology, Genetics & Heredity, Biomedical and clinical sciences, Health sciences
Abstract

Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.

Published
2016

6. Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes

Author

Deelen, Joris, Evans, Daniel S., Arking, Dan E., Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K., Biggs, Mary L., van der Spek, Ashley, Atzmon, Gil, Ware, Erin B., Sarnowski, Chloé, Smith, Albert V., Seppälä, Ilkka, Cordell, Heather J., Dose, Janina, Amin, Najaf, Arnold, Alice M., Ayers, Kristin L., Barzilai, Nir, Becker, Elizabeth J., Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C., Cubaynes, Sarah, Cummings, Steven R., Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D., Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B., Huisman, Martijn, Hurme, Mikko A., Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon L. R., Kingston, Andrew, Kirkwood, Thomas B. L., Launer, Lenore J., Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B., Nie, Chao, Nohr, Ellen A., Orwoll, Eric S., Perls, Thomas T., Province, Michael A., Psaty, Bruce M., Raitakari, Olli T., Reinders, Marcel J. T., Robine, Jean-Marie, Rotter, Jerome I., Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild I. A., Taylor, Kent D., Uitterlinden, André G., van der Flier, Wiesje, van der Lee, Sven J., van Duijn, Cornelia M., van Heemst, Diana, Vaupel, James W., Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P., Lunetta, Kathryn L., Slagboom, P. Eline, and Murabito, Joanne M.

Published
2021
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11. Introduction

Author

Christiansen, Lene Bull, primary, Galal, Lise Paulsen, additional, and Hvenegård-Lassen, Kirsten, additional

Published
2020
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13. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans.

Author

Mangino, Massimo, Hwang, Shih-Jen, Spector, Timothy, Hunt, Steven, Kimura, Masayuki, Fitzpatrick, Annette, Christiansen, Lene, Petersen, Inge, Elbers, Clara, Harris, Tamara, Chen, Wei, Srinivasan, Sathanur, Kark, Jeremy, Benetos, Athanase, El Shamieh, Said, Visvikis-Siest, Sophie, Christensen, Kaare, Berenson, Gerald, Valdes, Ana, Viñuela, Ana, Garcia, Melissa, Arnett, Donna, Broeckel, Ulrich, Province, Michael, Pankow, James, Kammerer, Candace, Liu, Yongmei, Nalls, Michael, Tishkoff, Sarah, Thomas, Fridtjof, Psaty, Bruce, Bis, Joshua, Taylor, Kent, Smith, Erin, Schork, Nicholas, Levy, Daniel, Aviv, Abraham, Ziv, Elad, and Rotter, Jerome

Subjects
Genome-Wide Association Study, Humans, Kruppel-Like Transcription Factors, Telomere, Telomere Homeostasis, Telomere-Binding Proteins
Abstract

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Published
2012

27. Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: Cross sectional and longitudinal studies

Author

Soerensen, Mette, Dato, Serena, Tan, Qihua, Thinggaard, Mikael, Kleindorp, Rabea, Beekman, Marian, Jacobsen, Rune, Suchiman, H. Eka D., de Craen, Anton J.M., Westendorp, Rudi G.J., Schreiber, Stefan, Stevnsner, Tinna, Bohr, Vilhelm A., Slagboom, P. Eline, Nebel, Almut, Vaupel, James W., Christensen, Kaare, McGue, Matt, and Christiansen, Lene

Published
2012
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30. Polygenic Risk Score Prediction for Endometriosis

Author

Kloeve-Mogensen, Kirstine, primary, Rohde, Palle Duun, additional, Twisttmann, Simone, additional, Nygaard, Marianne, additional, Koldby, Kristina Magaard, additional, Steffensen, Rudi, additional, Dahl, Christian Møller, additional, Rytter, Dorte, additional, Overgaard, Michael Toft, additional, Forman, Axel, additional, Christiansen, Lene, additional, and Nyegaard, Mette, additional

Published
2021
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37. DCAF4, a novel gene associated with leucocyte telomere length

Author

Mangino, Massimo, Christiansen, Lene, Stone, Rivka, Hunt, Steven C, Horvath, Kent, Eisenberg, Dan T A, Kimura, Masayuki, Petersen, Inge, Kark, Jeremy D, Herbig, Utz, Reiner, Alex P, Benetos, Athanase, Codd, Veryan, Nyholt, Dale R, Sinnreich, Ronit, Christensen, Kaare, Nassar, Hisham, Hwang, Shih-Jen, Levy, Daniel, Bataille, Veronique, Fitzpatrick, Annette L, Chen, Wei, Berenson, Gerald S, Samani, Nilesh J, Martin, Nicholas G, Tishkoff, Sarah, Schork, Nicholas J, Kyvik, Kirsten Ohm, Dalgård, Christine, Spector, Timothy D, and Aviv, Abraham

Published
2015
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39. FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

Author

Qi, Qibin, Kilpeläinen, Tuomas O., Downer, Mary K., Tanaka, Toshiko, Smith, Caren E., Sluijs, Ivonne, Sonestedt, Emily, Chu, Audrey Y., Renström, Frida, Lin, Xiaochen, Ängquist, Lars H., Huang, Jinyan, Liu, Zhonghua, Li, Yanping, Asif Ali, Muhammad, Xu, Min, Ahluwalia, Tarunveer Singh, Boer, Jolanda M.A., Chen, Peng, Daimon, Makoto, Eriksson, Johan, Perola, Markus, Friedlander, Yechiel, Gao, Yu-Tang, Heppe, Denise H.M., Holloway, John W., Houston, Denise K., Kanoni, Stavroula, Kim, Yu-Mi, Laaksonen, Maarit A., Jääskeläinen, Tiina, Lee, Nanette R., Lehtimäki, Terho, Lemaitre, Rozenn N., Lu, Wei, Luben, Robert N., Manichaikul, Ani, Männistö, Satu, Marques-Vidal, Pedro, Monda, Keri L., Ngwa, Julius S., Perusse, Louis, van Rooij, Frank J.A., Xiang, Yong-Bing, Wen, Wanqing, Wojczynski, Mary K, Zhu, Jingwen, Borecki, Ingrid B., Bouchard, Claude, Cai, Qiuyin, Cooper, Cyrus, Dedoussis, George V., Deloukas, Panos, Ferrucci, Luigi, Forouhi, Nita G., Hansen, Torben, Christiansen, Lene, Hofman, Albert, Johansson, Ingegerd, Jørgensen, Torben, Karasawa, Shigeru, Khaw, Kay-Tee, Kim, Mi-Kyung, Kristiansson, Kati, Li, Huaixing, Lin, Xu, Liu, Yongmei, Lohman, Kurt K., Long, Jirong, Mikkilä, Vera, Mozaffarian, Dariush, North, Kari, Pedersen, Oluf, Raitakari, Olli, Rissanen, Harri, Tuomilehto, Jaakko, van der Schouw, Yvonne T., Uitterlinden, André G., Zillikens, M. Carola, Franco, Oscar H., Shyong Tai, E., Ou Shu, Xiao, Siscovick, David S., Toft, Ulla, Verschuren, W.M. Monique, Vollenweider, Peter, Wareham, Nicholas J., Witteman, Jacqueline C.M., Zheng, Wei, Ridker, Paul M., Kang, Jae H., Liang, Liming, Jensen, Majken K., Curhan, Gary C., Pasquale, Louis R., Hunter, David J., Mohlke, Karen L., Uusitupa, Matti, Cupples, L. Adrienne, Rankinen, Tuomo, Orho-Melander, Marju, Wang, Tao, Chasman, Daniel I., Franks, Paul W., Sørensen, Thorkild I.A., Hu, Frank B., Loos, Ruth J. F., Nettleton, Jennifer A., and Qi, Lu

Published
2014
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40. Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

Author

Soerensen, Mette, Dato, Serena, Tan, Qihua, Thinggaard, Mikael, Kleindorp, Rabea, Beekman, Marian, Suchiman, H. Eka D., Jacobsen, Rune, McGue, Matt, Stevnsner, Tinna, Bohr, Vilhelm A., de Craen, Anton J. M., Westendorp, Rudi G. J., Schreiber, Stefan, Slagboom, P. Eline, Nebel, Almut, Vaupel, James W., Christensen, Kaare, and Christiansen, Lene

Published
2013
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41. Global Gene Expression Profiling and Transcription Factor Network Analysis of Cognitive Aging in Monozygotic Twins

Author

Mohammadnejad, Afsaneh, primary, Li, Weilong, additional, Lund, Jesper Beltoft, additional, Li, Shuxia, additional, Larsen, Martin J., additional, Mengel-From, Jonas, additional, Michel, Tanja Maria, additional, Christiansen, Lene, additional, Christensen, Kaare, additional, Hjelmborg, Jacob, additional, Baumbach, Jan, additional, and Tan, Qihua, additional

Published
2021
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42. Genetic meta-analysis of twin birth weight shows high genetic correlation with singleton birth weight

Author

Beck, Jeffrey J, primary, Pool, René, additional, van de Weijer, Margot, additional, Chen, Xu, additional, Krapohl, Eva, additional, Gordon, Scott D, additional, Nygaard, Marianne, additional, Debrabant, Birgit, additional, Palviainen, Teemu, additional, van der Zee, Matthijs D, additional, Baselmans, Bart, additional, Finnicum, Casey T, additional, Yi, Lu, additional, Lundström, Sebastian, additional, van Beijsterveldt, Toos, additional, Christiansen, Lene, additional, Heikkilä, Kauko, additional, Kittelsrud, Julie, additional, Loukola, Anu, additional, Ollikainen, Miina, additional, Christensen, Kaare, additional, Martin, Nicholas G, additional, Plomin, Robert, additional, Nivard, Michel, additional, Bartels, Meike, additional, Dolan, Conor, additional, Willemsen, Gonneke, additional, de Geus, Eco, additional, Almqvist, Catarina, additional, Magnusson, Patrik K E, additional, Mbarek, Hamdi, additional, Ehli, Erik A, additional, Boomsma, Dorret I, additional, and Hottenga, Jouke-Jan, additional

Published
2021
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45. A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the cohorts for heart and aging research in genomic epidemiology consortium

Author

Newman, Anne B., Walter, Stefan, Lunetta, Kathryn L., Garcia, Melissa E., Slagboom, Eline, Christensen, Kaare, Arnold, Alice M., Aspelund, Thor, Aulchenko, Yurii S., Benjamin, Emelia J., Christiansen, Lene, D'Agostino, Ralph B., Sr., Fitzpatrick, Annette L., Franceschini, Nora, Glazer, Nicole L., Gudnason, Vilmundur, Hofman, Albert, Kaplan, Robert, Karasik, David, Kelly-Hayes, Margaret, Kiel, Douglas E., Launer, Lenore J., Marciante, Kristin D., Massaro, Joseph M., Miljkovic, Iva, Nalls, Michael A., Hernandez, Dena, Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome, Seshadri, Sudha, Smith, Albert V., Taylor, Kent D., Tiemeier, Henning, Uh, Hae-Won, Uitterlinden, Andre G., Vaupel, James W., Walston, Jeremy, Westendorp, Rudi G.J., Harris, Tamara B., Lumley, Thomas, van Duijn, Cornelia M., and Murabito, Joanne M.

Subjects
Genomics -- Research, Single nucleotide polymorphisms -- Research, Longevity -- Health aspects, Longevity -- Genetic aspects, Health, Seniors
Abstract

Background. Genome-wide association studies (GWAS) may yield insights into longevity. Methods. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/ Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. Results. There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x [10.sup.-8]. Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x [10.sup.-7] for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. Conclusion. Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings. Key Words: Longevity--Genome-wide association study--Meta-analysis. doi: 10.1093/gerona/glq028

Published
2010

46. A variant in the fat mass and obesity-associated gene (FTO) and variants near the melanocortin-4 receptor gene (MC4R) do not influence dietary intake

Author

Hasselbalch, Ann L., Angquist, Lars, Christiansen, Lene, Heitmann, Berit L., Kyvik, Kirsten O., and Sorensen, Thorkild I.A.

Subjects
Food consumption -- Research, Obesity gene -- Research, Food/cooking/nutrition
Abstract

We investigated the role of the fat mass and obesity associated gene (FTO) and variants near the melanocortin-4 receptor gene (MC4R) in modulating habitual intake of total energy and macronutrients, glycemic index, glycemic load, dietary energy density, and energy from 20 food groups in adults. In a population-based sample of 756 healthy adult twin pairs, we studied associations between FTO rs9939609, near-MC4R rs12970134, rs17700633, and rs17782313 single nucleotide polymorphisms (SNP) and habitual dietary intake. Habitual dietary intake was assessed by a 247-question FFQ. Nontransformed variables and variables transformed by natural logarithm were analyzed by linear regression and dichotomized variables were analyzed by logistic regression. FTO SNP rs9939609 was not associated with habitual dietary intake. For the near-MC4R SNP rs12970134 and rs17700633, we found significant positive associations with intake of energy from whole grains (P [greater than or equal to] 0.04). These associations did not remain significant after controlling for multiple testing. The outcome of this study indicates that polymorphisms in the FTO gene and near the MC4R gene do not have a role in regulating food intake and preference for specific food items. doi: 10.3945/jn.109.114439

Published
2010

48. Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

Author

Deelen, Joris, Beekman, Marian, Uh, Hae-Won, Broer, Linda, Ayers, Kristin L., Tan, Qihua, Kamatani, Yoichiro, Bennet, Anna M., Tamm, Riin, Trompet, Stella, Gubjartsson, Daníel F., Flachsbart, Friederike, Rose, Giuseppina, Viktorin, Alexander, Fischer, Krista, Nygaard, Marianne, Cordell, Heather J., Crocco, Paolina, van den Akker, Erik B., Böhringer, Stefan, Helmer, Quinta, Nelson, Christopher P., Saunders, Gary I., Alver, Maris, Andersen-Ranberg, Karen, Breen, Marie E., van der Breggen, Ruud, Caliebe, Amke, Capri, Miriam, Cevenini, Elisa, Collerton, Joanna C., Dato, Serena, Davies, Karen, Ford, Ian, Gampe, Jutta, Garagnani, Paolo, de Geus, Eco J.C., Harrow, Jennifer, van Heemst, Diana, Heijmans, Bastiaan T., Heinsen, Femke-Anouska, Hottenga, Jouke-Jan, Hofman, Albert, Jeune, Bernard, Jonsson, Palmi V., Lathrop, Mark, Lechner, Doris, Martin-Ruiz, Carmen, Mcnerlan, Susan E., Mihailov, Evelin, Montesanto, Alberto, Mooijaart, Simon P., Murphy, Anne, Nohr, Ellen A., Paternoster, Lavinia, Postmus, Iris, Rivadeneira, Fernando, Ross, Owen A., Salvioli, Stefano, Sattar, Naveed, Schreiber, Stefan, Stefánsson, Hreinn, Stott, David J., Tiemeier, Henning, Uitterlinden, André G., Westendorp, Rudi G.J., Willemsen, Gonneke, Samani, Nilesh J., Galan, Pilar, Sørensen, Thorkild I.A., Boomsma, Dorret I., Jukema, J. Wouter, Rea, Irene Maeve, Passarino, Giuseppe, de Craen, Anton J.M., Christensen, Kaare, Nebel, Almut, Stefánsson, Kári, Metspalu, Andres, Magnusson, Patrik, Blanché, Hélène, Christiansen, Lene, Kirkwood, Thomas B.L., van Duijn, Cornelia M., Franceschi, Claudio, Houwing-Duistermaat, Jeanine J., and Slagboom, P. Eline

Published
2014
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49. Risk of metabolic syndrome and diabetes among young twins and singletons in Guinea-Bissau

Author

Bjerregaard-Andersen, Morten, Hansen, Lone, da Silva, Leontina I., Joaquim, Luis C., Hennild, Ditte E., Christiansen, Lene, Aaby, Peter, Benn, Christine S., Christensen, Kaare, Sodemann, Morten, Jensen, Dorte M., and Beck-Nielsen, Henning

Subjects
Guinea-Bissau -- Health aspects, Twins -- Health aspects -- Demographic aspects, Metabolic diseases -- Risk factors -- Demographic aspects, Health
Abstract

OBJECTIVE--Twins in Africa may be at increased risk of metabolic disorders due to strained conditions in utero, including high exposure to infections. We studied metabolic syndrome (MS) and diabetes mellitus [...]

Published
2013
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50. Novel DNA methylation marker discovery by assumption‐free genome‐wide association analysis of cognitive function in twins

Author

Mohammadnejad, Afsaneh, primary, Soerensen, Mette, additional, Baumbach, Jan, additional, Mengel‐From, Jonas, additional, Li, Weilong, additional, Lund, Jesper, additional, Li, Shuxia, additional, Christiansen, Lene, additional, Christensen, Kaare, additional, Hjelmborg, Jacob V. B., additional, and Tan, Qihua, additional

Published
2021
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