Genetic diversity is a predictor of mortality in humans

BMC Genetics

Dan E Arking^2,23  Thomas Lumley⁹  Thomas Kocher^3,34  Henning Tiemeier²  David A Bennett^1,11  Ian J Deary^1,15  Stefania Bandinelli^1,13  David R Weir^2,26  Andrew B Singleton^2,20  Joanne M Murabito^3,32  Lenore Launer⁸  Hans J Grabe^2,27  Roberto Lorbeer⁵  Georg Homuth^2,21  André Uitterlinden^1,16  Mohammed Arfan Ikram^1,19  Nese Direk⁴  Denis A Evans^2,28  Philip L De Jager^1,10  John M Starr^2,25  Paul Redmond^1,15  David C Liewald^3,35  Michael Allerhand^3,35  Luigi Ferrucci⁷  Wei Zhao^1,12  Sharon LR Kardia^1,12  Jessica D Faul^2,26  Yongmei Liu³  Melissa Garcia^1,14  Douglas P Kiel⁶  David Karasik⁶  Hanyue Li¹  Tamara B Harris⁸  Gudny Eiriksdottir^2,22  Vilmundur Gudnason^2,24  Bruce M Psaty^2,29  Junko Oshima^1,17  Anish Scaria⁹  Nora Franceschini^1,18  James S Pankow^3,30  Josef Coresh^3,33  Alexander Teumer⁵  Saira Saeed Mirza⁴  Lei Yu^1,11  Gail Davies^1,15  Toshiko Tanaka⁷  Jennifer A Smith^1,12  Mike Nalls^2,20  Kathryn L Lunetta¹  Albert Vernon Smith^2,24  Jennifer A Brody^3,31  Nathan A Bihlmeyer^2,23 

[1] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA;Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands;Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA;Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands;Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany;Institute for Aging Research, Hebrew Senior Life, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Cambridge, MA, USA;Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA;National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;Department of Statistics, University of Auckland, 303.325 Science Centre, Private Bag 92019, Auckland 1142, New Zealand;Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA;Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA;Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy;Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;Department of Psychology, The University of Edinburgh, Edinburgh, UK;Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands;Department of Pathology, University of Washington, Seattle, WA, USA;Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill 27514, NC, USA;Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands;Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany;Icelandic Heart Association, Kopavogur, Iceland;McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, BRB Room 447, 733 N. Broadway St, Baltimore 21205, MD, USA;University of Iceland, Reykjavik, Iceland;Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, UK;Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA;German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany;Rush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA;Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA;Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA;Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA;Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA;Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;Unit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald, Germany;Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK

关键词: GWAS;    Survival;    Human;    Heterozygosity;   

Others  :  1121340
DOI  :  10.1186/s12863-014-0159-7

 received in 2014-07-22, accepted in 2014-12-19,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Bihlmeyer et al.; licensee Biomed Central.

【 图 表 】

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