Genetic diversity is a predictor of mortality in humans

Nathan A. Bihlmeyer, Jennifer A. Brody, Albert V ernon Smith, Kathryn L. Lunetta, Mike Nalls, Jennifer A. Smith, Toshiko Tanaka, Gail Davies, Lei Yu, Saira S aeed Mirza, Alexander Teumer, Josef Coresh, James S. Pankow, Nora Franceschini, Anish Scaria, Junko Oshima, Bruce M. Psaty, Vilmundur Gudnason, Gudny Eiriksdottir, Tamara B. Harris & 32 others Hanyue 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 A rfan 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 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)
Pages (from-to)159
Number of pages1
JournalBMC Genetics
Volume15
DOIs
StatePublished - 2014

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Sample Size
Survival
Mortality
Health
Population Genetics
Population Dynamics
Population
Meta-Analysis
Cause of Death
Cardiovascular Diseases
Alleles
Observation
Genome
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bihlmeyer, N. A., Brody, J. A., Smith, A. V. E., Lunetta, K. L., Nalls, M., Smith, J. A., ... Arking, D. (2014). Genetic diversity is a predictor of mortality in humans. BMC Genetics, 15, 159. https://doi.org/10.1186/s12863-014-0159-7

Genetic diversity is a predictor of mortality in humans. / Bihlmeyer, Nathan A.; Brody, Jennifer A.; Smith, Albert V ernon; Lunetta, Kathryn L.; Nalls, Mike; Smith, Jennifer A.; Tanaka, Toshiko; Davies, Gail; Yu, Lei; Mirza, Saira S aeed; Teumer, Alexander; Coresh, Josef; Pankow, James S.; Franceschini, Nora; Scaria, Anish; Oshima, Junko; Psaty, Bruce M.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Harris, Tamara B.; Li, Hanyue; Karasik, David; Kiel, Douglas P.; Garcia, Melissa; Liu, Yongmei; Faul, Jessica D.; Kardia, Sharon L r; Zhao, Wei; Ferrucci, Luigi; Allerhand, Michael; Liewald, David C.; Redmond, Paul; Starr, John M.; De Jager, Philip L.; Evans, Denis A.; Direk, Nese; Ikram, Mohammed A rfan; Uitterlinden, André; Homuth, Georg; Lorbeer, Roberto; Grabe, Hans J.; Launer, Lenore; Murabito, Joanne M.; Singleton, Andrew B.; Weir, David R.; Bandinelli, Stefania; Deary, Ian J.; Bennett, David A.; Tiemeier, Henning; Kocher, Thomas; Lumley, Thomas; Arking, Dan.

In: BMC Genetics, Vol. 15, 2014, p. 159.

Research output: Contribution to journalArticle

Bihlmeyer, NA, Brody, JA, Smith, AVE, Lunetta, KL, Nalls, M, Smith, JA, Tanaka, T, Davies, G, Yu, L, Mirza, SSA, 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, MAR, 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, D 2014, 'Genetic diversity is a predictor of mortality in humans', BMC Genetics, vol. 15, pp. 159. https://doi.org/10.1186/s12863-014-0159-7
Bihlmeyer NA, Brody JA, Smith AVE, Lunetta KL, Nalls M, Smith JA et al. Genetic diversity is a predictor of mortality in humans. BMC Genetics. 2014;15:159. https://doi.org/10.1186/s12863-014-0159-7
Bihlmeyer, Nathan A. ; Brody, Jennifer A. ; Smith, Albert V ernon ; Lunetta, Kathryn L. ; Nalls, Mike ; Smith, Jennifer A. ; Tanaka, Toshiko ; Davies, Gail ; Yu, Lei ; Mirza, Saira S aeed ; Teumer, Alexander ; Coresh, Josef ; Pankow, James S. ; Franceschini, Nora ; Scaria, Anish ; Oshima, Junko ; Psaty, Bruce M. ; Gudnason, Vilmundur ; Eiriksdottir, Gudny ; Harris, Tamara B. ; Li, Hanyue ; Karasik, David ; Kiel, Douglas P. ; Garcia, Melissa ; Liu, Yongmei ; Faul, Jessica D. ; Kardia, Sharon L r ; Zhao, Wei ; Ferrucci, Luigi ; Allerhand, Michael ; Liewald, David C. ; Redmond, Paul ; Starr, John M. ; De Jager, Philip L. ; Evans, Denis A. ; Direk, Nese ; Ikram, Mohammed A rfan ; Uitterlinden, André ; Homuth, Georg ; Lorbeer, Roberto ; Grabe, Hans J. ; Launer, Lenore ; Murabito, Joanne M. ; Singleton, Andrew B. ; Weir, David R. ; Bandinelli, Stefania ; Deary, Ian J. ; Bennett, David A. ; Tiemeier, Henning ; Kocher, Thomas ; Lumley, Thomas ; Arking, Dan. / Genetic diversity is a predictor of mortality in humans. In: BMC Genetics. 2014 ; Vol. 15. pp. 159.
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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.",
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T1 - Genetic diversity is a predictor of mortality in humans

AU - Bihlmeyer, Nathan A.

AU - Brody, Jennifer A.

AU - Smith, Albert V ernon

AU - Lunetta, Kathryn L.

AU - Nalls, Mike

AU - Smith, Jennifer A.

AU - Tanaka, Toshiko

AU - Davies, Gail

AU - Yu, Lei

AU - Mirza, Saira S aeed

AU - Teumer, Alexander

AU - Coresh, Josef

AU - Pankow, James S.

AU - Franceschini, Nora

AU - Scaria, Anish

AU - Oshima, Junko

AU - Psaty, Bruce M.

AU - Gudnason, Vilmundur

AU - Eiriksdottir, Gudny

AU - Harris, Tamara B.

AU - Li, Hanyue

AU - Karasik, David

AU - Kiel, Douglas P.

AU - Garcia, Melissa

AU - Liu, Yongmei

AU - Faul, Jessica D.

AU - Kardia, Sharon L r

AU - Zhao, Wei

AU - Ferrucci, Luigi

AU - Allerhand, Michael

AU - Liewald, David C.

AU - Redmond, Paul

AU - Starr, John M.

AU - De Jager, Philip L.

AU - Evans, Denis A.

AU - Direk, Nese

AU - Ikram, Mohammed A rfan

AU - Uitterlinden, André

AU - Homuth, Georg

AU - Lorbeer, Roberto

AU - Grabe, Hans J.

AU - Launer, Lenore

AU - Murabito, Joanne M.

AU - Singleton, Andrew B.

AU - Weir, David R.

AU - Bandinelli, Stefania

AU - Deary, Ian J.

AU - Bennett, David A.

AU - Tiemeier, Henning

AU - Kocher, Thomas

AU - Lumley, Thomas

AU - Arking, Dan

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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