Title | Genetic diversity is a predictor of mortality in humans. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Bihlmeyer, NA, Brody, JA, Smith, AVernon, Lunetta, KL, Nalls, M, Smith, JA, Tanaka, T, Davies, G, Yu, L, Mirza, SSaeed, Teumer, A, Coresh, J, Pankow, JS, Franceschini, N, Scaria, A, Oshima, J, Psaty, BM, Gudnason, V, Eiriksdottir, G, Harris, TB, Li, H, Karasik, D, Kiel, DP, Garcia, M, Liu, Y, Faul, JD, Kardia, SLr, Zhao, W, Ferrucci, L, Allerhand, M, Liewald, DC, Redmond, P, Starr, JM, De Jager, PL, Evans, DA, Direk, N, Ikram, MArfan, Uitterlinden, A, Homuth, G, Lorbeer, R, Grabe, HJ, Launer, L, Murabito, JM, Singleton, AB, Weir, DR, Bandinelli, S, Deary, IJ, Bennett, DA, Tiemeier, H, Kocher, T, Lumley, T, Arking, DE |
Journal | BMC Genet |
Volume | 15 |
Pagination | 159 |
Date Published | 2014 |
ISSN | 1471-2156 |
Keywords | Genome-Wide Association Study, Heterozygote, Humans, Mortality, Polymorphism, Single Nucleotide, Proportional Hazards Models |
Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>RESULTS: </b>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%.</p><p><b>CONCLUSIONS: </b>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.</p> |
DOI | 10.1186/s12863-014-0159-7 |
Alternate Journal | BMC Genet. |
PubMed ID | 25543667 |
PubMed Central ID | PMC4301661 |
Grant List | 5T32GM07814 / GM / NIGMS NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R24 AG042328 / AG / NIA NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States |