Genetic diversity is a predictor of mortality in humans

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. HarrisHanyue Li, David Karasik, Douglas P. Kiel, Melissa Garcia, Yongmei Liu, Jessica D. Faul, Sharon L.R. 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number159
JournalBMC genetics
Volume15
Issue number1
DOIs
StatePublished - 2014

Keywords

  • GWAS
  • Heterozygosity
  • Human
  • Survival

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Bihlmeyer, N. A., Brody, J. A., Smith, A. V., Lunetta, K. L., Nalls, M., Smith, J. A., Tanaka, T., Davies, G., Yu, L., Mirza, S. S., Teumer, A., Coresh, J., Pankow, J. S., Franceschini, N., Scaria, A., Oshima, J., Psaty, B. M., Gudnason, V., Eiriksdottir, G., ... Arking, D. E. (2014). Genetic diversity is a predictor of mortality in humans. BMC genetics, 15(1), [159]. https://doi.org/10.1186/s12863-014-0159-7