Evidence map›Paper›PMID 25543667›Full record

SynthesisBMC genetics2014

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 and 42 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors.

Nathan A BihlmeyerPredoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. nbihlme1@jhmi.edu.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA. jeco@u.washington.edu.
Albert Vernon SmithIcelandic Heart Association, Kopavogur, Iceland. albert@hjarta.is.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA. klunetta@bu.edu.
Mike NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. nallsm@mail.nih.gov.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. smjenn@umich.edu.
Toshiko TanakaTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA. tanakato@mail.nih.gov.
Gail DaviesCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. Gail.Davies@ed.ac.uk.
Lei YuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. Lei_Yu@rush.edu.
Saira Saeed MirzaDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. s.mirza@erasmusmc.nl.
Alexander TeumerInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. ateumer@uni-greifswald.de.
Josef CoreshDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. coresh@jhu.edu.
James S PankowDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. panko001@umn.edu.
Nora FranceschiniDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA. noraf@unc.edu.
Anish ScariaDepartment of Statistics, University of Auckland, 303.325 Science Centre, Private Bag 92019, Auckland, 1142, New Zealand. a.scaria@uq.edu.au.
Junko OshimaDepartment of Pathology, University of Washington, Seattle, WA, USA. picard@u.washington.edu.
Bruce M PsatyDepartments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. psaty@u.washington.edu.
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland. vgudnason@hjarta.is.
Gudny EiriksdottirIcelandic Heart Association, Kopavogur, Iceland. Gudny@hjarta.is.
Tamara B HarrisNational Institute on Aging, National Institutes of Health, Bethesda, MD, USA. harris99@nia.nih.gov.
Hanyue LiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA. hyue@bu.edu.
David KarasikInstitute 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.
Douglas P KielInstitute 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.
Melissa GarciaLaboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. garciamel@mail.nih.gov.
Yongmei LiuDepartment of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA. yoliu@wfubmc.edu.
Jessica D FaulSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. jfaul@umich.edu.
Sharon Lr KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. skardia@umich.edu.
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. zhaowei@umich.edu.
Luigi FerrucciTranslational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA. FerrucciLu@grc.nia.nih.gov.
Michael AllerhandCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. m.allerhand@ed.ac.uk.
David C LiewaldCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. dave.liewald@ed.ac.uk.
Paul RedmondDepartment of Psychology, The University of Edinburgh, Edinburgh, UK. paul.redmond@ed.ac.uk.
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. jstarr@staffmail.ed.ac.uk.
Philip L De JagerProgram in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. pdejager@rics.bwh.harvard.edu.
Denis A EvansRush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. Denis_Evans@rush.edu.
Nese DirekDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. n.direk@erasmusmc.nl.
Mohammed Arfan IkramDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. m.a.ikram@erasmusmc.nl.
André UitterlindenDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. a.g.uitterlinden@erasmusmc.nl.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. Georg.homuth@uni-greifswald.de.
Roberto LorbeerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. roberto.lorbeer@uni-greifswald.de.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Greifswald, Germany. grabeh@uni-greifswald.de.
Lenore LaunerNational Institute on Aging, National Institutes of Health, Bethesda, MD, USA. LaunerL@nia.nih.gov.
Joanne M MurabitoThe National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA. murabito@bu.edu.
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. singleta@mail.nih.gov.
David R WeirSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. dweir@umich.edu.
Stefania BandinelliGeriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy. stefania.bandinelli@asf.toscana.it.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK. iand@staffmail.ed.ac.uk.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. dbennett@rush.edu.
Henning TiemeierDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. h.tiemeier@erasmusmc.nl.
Thomas KocherUnit of Periodontology, Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald, Germany. kocher@uni-greifswald.de.
Thomas LumleyDepartment of Statistics, University of Auckland, 303.325 Science Centre, Private Bag 92019, Auckland, 1142, New Zealand. t.lumley@auckland.ac.nz.
Dan E ArkingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, BRB Room 447, 733 N. Broadway St, Baltimore, MD, 21205, USA. arking@jhmi.edu.

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
RISK FACTORS FOR VERTEBRAL FRACTURE AND BONE LOSSR01AR041398 · NIAMS · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI KIEL, DOUGLAS P. · 1991 to 2025
$16.1M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Predoctoral Training Program in Human GeneticsT32GM007814 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 1985 to 2021
$10.6M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
Intramural NIH HHS Z01 AG000949Intramural NIH HHS Z01 AG007390Medical Research Council G0700704Medical Research Council MR/K026992/1NCATS NIH HHS UL1 TR000124NCRR NIH HHS UL1 RR025005NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004402NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U01 HL080295NIAMS NIH HHS R01 AR041398NIA NIH HHS N01 AG012100NIA NIH HHS N01 AG062101NIA NIH HHS N01 AG062103NIA NIH HHS N01 AG062106NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG029451NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG032098NIA NIH HHS R24 AG042328NIA NIH HHS R56 AG023629NIA NIH HHS RC2 AG036495NIA NIH HHS RC4 AG039029NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG009740NIDDK NIH HHS P30 DK063491NIGMS NIH HHS 5T32GM07814NIGMS NIH HHS T32 GM007814NIMHD NIH HHS R01 MD009164
6 · The paper itself

Abstract

backgroundIt 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.

resultsWe 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%.

conclusionsThis 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.

Indexed as

Polymorphism, Single NucleotideGenome-Wide Association StudyHeterozygoteHumansMortalityProportional Hazards Models

Identifiers

PMID25543667
PMCPMC4301661

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.