Year: 2014
Type: article
Abstract: BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.
Source: BMC Genetics
Authors: Nathan A Bihlmeyer, Jennifer A Brody, Albert Vernon Smith, Kathryn L Lunetta, Mike Nalls, Jennifer A Smith, Toshiko Tanaka, Gail Davies, Lei Yu, Saira Saeed Mirza, Alexander Teumer, Josef Coresh, James S Pankow, Nora Franceschini, Anish Scaria, Junko Oshima, Bruce M Psaty, Vilmundur Gudnason, Gudny Eiriksdottir, Tamara B Harris, Hanyue Li, David Karasik, Douglas P Kiel, Melissa Garcia, Yongmei Liu, Jessica D Faul, Sharon LR Kardia, Wei Zhao, Luigi Ferrucci, Michael Allerhand, David C Liewald, Paul Redmond, John M Starr, Philip L De Jager, Denis A Evans, Nese Direk, Mohammed Arfan Ikram, André Uitterlinden, Georg Homuth, Roberto Lorbeer, Hans J Grabe, Lenore Launer, Joanne M Murabito, Andrew B Singleton, David R Weir, Stefania Bandinelli, Ian J Deary, David A Bennett, Henning Tiemeier, Thomas Kocher, Thomas Lumley, Dan E Arking
Institutions: Johns Hopkins University, Johns Hopkins Medicine, University of Washington, University of Iceland, Icelandic Heart Association, Boston University, National Heart, Lung, and Blood Institute, Framingham Heart Study, National Institutes of Health, National Institute on Aging, University of Michigan, University of Edinburgh, Rush University Medical Center, Erasmus MC, Universitätsmedizin Greifswald, University of Minnesota, University of North Carolina at Chapel Hill, University of Auckland, Beth Israel Deaconess Medical Center, Harvard University, Hebrew SeniorLife, Wake Forest University Health Sciences, Wake Forest University, Institute for Social Research, Alzheimer Scotland, Brigham and Women's Hospital, German Center for Neurodegenerative Diseases, Azienda Sanitaria di Firenze
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,170
Funders: National Science Foundation, Brigham and Women's Hospital, School of Medicine, Boston University, Johns Hopkins University, Rush University, School of Public Health, University of Michigan, University of Edinburgh, Hjartavernd, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, University of California, San Francisco, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1023702118, G1052397333, G1097528416, Epidemiologic Study of Neural Reserve and Neurobiology of Aging, G1135917780, G1220223050, G1224608327, G1243299691, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1401438683, G1438302022, DYNAMICS OF HEALTH,AGING, AND BODY COMPOSITION, G1460387277, G1466586219, G1527150935, THE AGES STUDY - THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENUM, CORONARY HEART DISEASE AND STROKE, G1691174148, Genetic Epidemiology of Cognitive Decline in an Aging Population Sample, G1726490033, G173303992, G1941623656, Genome-wide case-only study of antihypertensive drug-gene interactions, G2070131968, DYNAMICS OF HEALTH, AGING, AND BODY COMPOSITION, Genetic Determinants of Visceral Adiposity, G2193588257, G2194386449, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G230712557, Health, Aging and Body Composition Study, G2391884931, Institute for Clinical and Translational Research (UL1), Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G250924255, G2555954497, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G2786044735, G2800149121, G2818629771, G2818913090, Exceptional Aging Across the Life Span: Framingham Study, G3007488127, G301743239, G3045517347, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3114902838, G3137375862, G3152385821, HEALTH ABC--COORDINATING UNIT, G3220743633, G322252321, UCLA Clinical and Translational Science Institute, International Registry of Werner Syndrome, G3402222819, G3410686264, G34347772, G3462919067, Predoctoral Training Program in Human Genetics, GWA for Gene-Environment Interaction Effects Influencing CHD, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4167445418, G4200864717, G4219624527, G423252844, G4247100892, Creating a National Resource for Genetic Research in Behavioral & Health Sciences, G457330776, G4622379297, G4660668308, G4824283243, Risk Factors, Pathology, and Clinical Expressions of AD, G4942589162, Rush Alzheimer's Disease Core Center, G5053595415, G5067462658, G5074086979, G5145575165, G5164707915, G5251985303, G5386252567, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G544148272, G5479317095, G5488312170, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G567847597, G573134505, G581887176, G5909482378, CHARGE consortium: omics discovery for CVD and aging phenotypes, CHS Events Follow-up Study, G6195637971, Expanding a National Resource for Genetic Research in Behavioral & Health Science, G6226795708, The Framingham Heart Study, G6548750934, G6552090923, G6706757010, G6832344490, G6902273418, G704562166, G7176672723, G7217924807, G7244861316, G7373387228, G7415749889, G764651519, G766700449, G766843672, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G777822606, CHS Events Follow-up Study, G806768229, G8068269535, Graduate Research Fellowship Program (GRFP), G824087253, G8260701975, G8267674335, Risk Factors, Pathology, and Clinical Expressions of AD, CHS-Transition Phase -268055222, G870807107, HISPANIC SECONDARY STROKE PREVENTION INITIATIVE, G8892155751, G9000027259, G9000046001, G9000069887, G9000124008, G9000139054, G9000155215, G9000268494, G9000294005, G9000296875, Novel Molecular Biomarkers of Bone Microarchitecture, Diabetes Research Center (DRC), Health and Retirement Study: Yrs 35-40, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G945304896
OpenAlex ID: W2161718157