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Genetic diversity is a predictor of mortality in humans.
Bihlmeyer, Nathan A; Brody, Jennifer A; Smith, Albert Vernon; Lunetta, Kathryn L; Nalls, Mike; Smith, Jennifer A; Tanaka, Toshiko; Davies, Gail; Yu, Lei; Mirza, Saira Saeed; 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 Lr; 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 Arfan; 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.
Afiliação
  • Bihlmeyer NA; Predoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. nbihlme1@jhmi.edu.
  • Brody JA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, BRB Room 447, 733 N. Broadway St, Baltimore, MD, 21205, USA. nbihlme1@jhmi.edu.
  • Smith AV; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA. jeco@u.washington.edu.
  • Lunetta KL; Icelandic Heart Association, Kopavogur, Iceland. albert@hjarta.is.
  • Nalls M; University of Iceland, Reykjavik, Iceland. albert@hjarta.is.
  • Smith JA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. klunetta@bu.edu.
  • Tanaka T; The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA. klunetta@bu.edu.
  • Davies G; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. nallsm@mail.nih.gov.
  • Yu L; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. smjenn@umich.edu.
  • Mirza SS; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA. tanakato@mail.nih.gov.
  • Teumer A; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. Gail.Davies@ed.ac.uk.
  • Coresh J; Department of Psychology, The University of Edinburgh, Edinburgh, UK. Gail.Davies@ed.ac.uk.
  • Pankow JS; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. Lei_Yu@rush.edu.
  • Franceschini N; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. s.mirza@erasmusmc.nl.
  • Scaria A; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. ateumer@uni-greifswald.de.
  • Oshima J; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. ateumer@uni-greifswald.de.
  • Psaty BM; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. coresh@jhu.edu.
  • Gudnason V; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. panko001@umn.edu.
  • Eiriksdottir G; Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA. noraf@unc.edu.
  • Harris TB; Department of Statistics, University of Auckland, 303.325 Science Centre, Private Bag 92019, Auckland, 1142, New Zealand. a.scaria@uq.edu.au.
  • Li H; Department of Pathology, University of Washington, Seattle, WA, USA. picard@u.washington.edu.
  • Karasik D; Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. psaty@u.washington.edu.
  • Kiel DP; Icelandic Heart Association, Kopavogur, Iceland. vgudnason@hjarta.is.
  • Garcia M; University of Iceland, Reykjavik, Iceland. vgudnason@hjarta.is.
  • Liu Y; Icelandic Heart Association, Kopavogur, Iceland. Gudny@hjarta.is.
  • Faul JD; National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. harris99@nia.nih.gov.
  • Kardia SL; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. hyue@bu.edu.
  • Zhao W; Institute for Aging Research, Hebrew Senior Life, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Cambridge, MA, USA. karasik@hsl.harvard.edu.
  • Ferrucci L; Institute for Aging Research, Hebrew Senior Life, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Cambridge, MA, USA. kiel@hsl.harvard.edu.
  • Allerhand M; Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. garciamel@mail.nih.gov.
  • Liewald DC; Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA. yoliu@wfubmc.edu.
  • Redmond P; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. jfaul@umich.edu.
  • Starr JM; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. skardia@umich.edu.
  • De Jager PL; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. zhaowei@umich.edu.
  • Evans DA; Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA. FerrucciLu@grc.nia.nih.gov.
  • Direk N; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. m.allerhand@ed.ac.uk.
  • Ikram MA; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. dave.liewald@ed.ac.uk.
  • Uitterlinden A; Department of Psychology, The University of Edinburgh, Edinburgh, UK. paul.redmond@ed.ac.uk.
  • Homuth G; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. jstarr@staffmail.ed.ac.uk.
  • Lorbeer R; Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, UK. jstarr@staffmail.ed.ac.uk.
  • Grabe HJ; Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. pdejager@rics.bwh.harvard.edu.
  • Launer L; Rush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. Denis_Evans@rush.edu.
  • Murabito JM; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. n.direk@erasmusmc.nl.
  • Singleton AB; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. m.a.ikram@erasmusmc.nl.
  • Weir DR; Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands. m.a.ikram@erasmusmc.nl.
  • Bandinelli S; Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands. m.a.ikram@erasmusmc.nl.
  • Deary IJ; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. a.g.uitterlinden@erasmusmc.nl.
  • Bennett DA; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. a.g.uitterlinden@erasmusmc.nl.
  • Tiemeier H; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. Georg.homuth@uni-greifswald.de.
  • Kocher T; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. roberto.lorbeer@uni-greifswald.de.
BMC Genet ; 15: 159, 2014 Dec 29.
Article em En | MEDLINE | ID: mdl-25543667
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único Idioma: En Ano de publicação: 2014 Tipo de documento: Article