A meta-analysis of genome-wide association studies identifies multiple longevity genes

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percenti...

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Veröffentlicht in:Nature communications Jg. 10; H. 1; S. 3669 - 14
Hauptverfasser: Deelen, Joris, Evans, Daniel S., Arking, Dan E., Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K., Biggs, Mary L., van der Spek, Ashley, Atzmon, Gil, Ware, Erin B., Sarnowski, Chloé, Smith, Albert V., Seppälä, Ilkka, Cordell, Heather J., Dose, Janina, Amin, Najaf, Arnold, Alice M., Ayers, Kristin L., Barzilai, Nir, Becker, Elizabeth J., Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C., Cubaynes, Sarah, Cummings, Steven R., Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D., Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B., Huisman, Martijn, Hurme, Mikko A., Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon L. R., Kingston, Andrew, Kirkwood, Thomas B. L., Launer, Lenore J., Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B., Nie, Chao, Nohr, Ellen A., Orwoll, Eric S., Perls, Thomas T., Province, Michael A., Psaty, Bruce M., Raitakari, Olli T., Reinders, Marcel J. T., Robine, Jean-Marie, Rotter, Jerome I., Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild I. A., Taylor, Kent D., Uitterlinden, André G., van der Flier, Wiesje, van der Lee, Sven J., van Duijn, Cornelia M., van Heemst, Diana, Vaupel, James W., Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P., Lunetta, Kathryn L., Slagboom, P. Eline, Murabito, Joanne M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 14.08.2019
Nature Publishing Group
Nature Portfolio
Schlagworte:
45/43
631/208/205/2138
631/443/7
692/499
692/699
Age
Apolipoprotein E
Apolipoprotein E2 - genetics
Apolipoprotein E4 - genetics
Association analysis
Endoplasmic Reticulum Chaperone BiP
Gene expression
Genes
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Heat-Shock Proteins - genetics
Humanities and Social Sciences
Humans
Life Sciences
Loci
Longevity
Longevity - genetics
Meta-analysis
multidisciplinary
Phenotypes
Science
Survival
ISSN:2041-1723, 2041-1723
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Abstract Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78 , associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity. Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78 .
AbstractList Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78 , associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
A meta-analysis of genome-wide association studies identifies multiple longevity genes Joris Deelen et al. # Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78 , associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity. Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78 .
Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
ArticleNumber 3669
Author van der Spek, Ashley
Becker, Elizabeth J.
Psaty, Bruce M.
Nygaard, Marianne
Gudnason, Vilmundur
van Duijn, Cornelia M.
Slagboom, P. Eline
Christiansen, Lene
Sebastiani, Paola
Arnold, Alice M.
Dose, Janina
Newman, Anne B.
Holstege, Henne
Jylhä, Marja
Seppälä, Ilkka
Amin, Najaf
Zheng, Wanlin
van Heemst, Diana
Zeng, Yi
Deelen, Joris
Vaupel, James W.
Lyytikäinen, Leo-Pekka
Hurme, Mikko A.
Robine, Jean-Marie
Kingston, Andrew
Wojczynski, Mary K.
Jagger, Carol
Lieb, Wolfgang
Nohr, Ellen A.
Murabito, Joanne M.
Christensen, Kaare
Arking, Dan E.
Lehtimäki, Terho
Barzilai, Nir
Beekman, Marian
Orwoll, Eric S.
Province, Michael A.
Davies, Karen
Smith, Jennifer
Cordell, Heather J.
Ye, Kenny
Cummings, Steven R.
Min, Junxia
Martin-Ruiz, Carmen
Kiel, Douglas P.
Ware, Erin B.
Kähönen, Mika
Weir, David
Kardia, Sharon L. R.
Taylor, Kent D.
Tesi, Niccolò
Deleuze, Jean-François
Nie, Chao
Raitakari, Olli T.
Perls, Thomas T.
Sørensen, Thorkild I. A.
Sarnowski, Chloé
Duncan, Rachel
van der Lee, Sven J.
Lunetta, Kathryn L.
Evans, Daniel S.
Cubaynes, Sarah
Franceschi, Clau
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  surname: Rotter
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  organization: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center
– sequence: 66
  givenname: Paola
  surname: Sebastiani
  fullname: Sebastiani, Paola
  organization: Department of Biostatistics, Boston University School of Public Health
– sequence: 67
  givenname: Jennifer
  orcidid: 0000-0002-3575-5468
  surname: Smith
  fullname: Smith, Jennifer
  organization: Institute for Social Research, Survey Research Center, University of Michigan, School of Public Health, Epidemiology, University of Michigan
– sequence: 68
  givenname: Thorkild I. A.
  orcidid: 0000-0003-4821-430X
  surname: Sørensen
  fullname: Sørensen, Thorkild I. A.
  organization: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, and Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, MRC Integrative Epidemiology Unit, Bristol University
– sequence: 69
  givenname: Kent D.
  orcidid: 0000-0002-2756-4370
  surname: Taylor
  fullname: Taylor, Kent D.
  organization: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Pediatrics, Harbor-UCLA Medical Center
– sequence: 70
  givenname: André G.
  orcidid: 0000-0002-7276-3387
  surname: Uitterlinden
  fullname: Uitterlinden, André G.
  organization: Department of Epidemiology, Erasmus MC, Department of Internal Medicine, Erasmus MC
– sequence: 71
  givenname: Wiesje
  surname: van der Flier
  fullname: van der Flier, Wiesje
  organization: Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC
– sequence: 72
  givenname: Sven J.
  orcidid: 0000-0003-1606-8643
  surname: van der Lee
  fullname: van der Lee, Sven J.
  organization: Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Department of Clinical Genetics, Amsterdam UMC
– sequence: 73
  givenname: Cornelia M.
  surname: van Duijn
  fullname: van Duijn, Cornelia M.
  organization: Department of Epidemiology, Erasmus MC, Nuffield Department of Population Health, University of Oxford
– sequence: 74
  givenname: Diana
  surname: van Heemst
  fullname: van Heemst, Diana
  organization: Department of Gerontology and Geriatrics, Leiden University Medical Center
– sequence: 75
  givenname: James W.
  surname: Vaupel
  fullname: Vaupel, James W.
  organization: Max Planck Institute for Demographic Research
– sequence: 76
  givenname: David
  orcidid: 0000-0002-1661-2402
  surname: Weir
  fullname: Weir, David
  organization: Institute for Social Research, Survey Research Center, University of Michigan
– sequence: 77
  givenname: Kenny
  orcidid: 0000-0002-1466-855X
  surname: Ye
  fullname: Ye, Kenny
  organization: Department of Epidemiology and Population Health, Albert Einstein College of Medicine
– sequence: 78
  givenname: Yi
  surname: Zeng
  fullname: Zeng, Yi
  organization: Center for Healthy Aging and Development Studies, National School of Development and Raissun Institute for Advanced Studies, Peking University, Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University
– sequence: 79
  givenname: Wanlin
  surname: Zheng
  fullname: Zheng, Wanlin
  organization: California Pacific Medical Center Research Institute
– sequence: 80
  givenname: Henne
  surname: Holstege
  fullname: Holstege, Henne
  organization: Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Department of Clinical Genetics, Amsterdam UMC, Delft Bioinformatics Lab, Delft University of Technology
– sequence: 81
  givenname: Douglas P.
  orcidid: 0000-0001-8474-0310
  surname: Kiel
  fullname: Kiel, Douglas P.
  organization: Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Broad Institute of MIT & Harvard
– sequence: 82
  givenname: Kathryn L.
  orcidid: 0000-0002-9268-810X
  surname: Lunetta
  fullname: Lunetta, Kathryn L.
  organization: Department of Biostatistics, Boston University School of Public Health
– sequence: 83
  givenname: P. Eline
  surname: Slagboom
  fullname: Slagboom, P. Eline
  email: P.Slagboom@lumc.nl
  organization: Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center
– sequence: 84
  givenname: Joanne M.
  surname: Murabito
  fullname: Murabito, Joanne M.
  email: murabito@bu.edu
  organization: NHLBI’s and Boston University’s Framingham Heart Study, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31413261$$D View this record in MEDLINE/PubMed
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Copyright The Author(s) 2019. corrected publication 2021
2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
The Author(s) 2019. corrected publication 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– notice: 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: The Author(s) 2019. corrected publication 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– reference: 33893282 - Nat Commun. 2021 Apr 23;12(1):2463. doi: 10.1038/s41467-021-22613-2.
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Snippet Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a...
A meta-analysis of genome-wide association studies identifies multiple longevity genes Joris Deelen et al. # Human longevity is heritable, but genome-wide...
Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of...
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SubjectTerms 45/43
631/208/205/2138
631/443/7
692/499
692/699
Age
Apolipoprotein E
Apolipoprotein E2 - genetics
Apolipoprotein E4 - genetics
Association analysis
Endoplasmic Reticulum Chaperone BiP
Gene expression
Genes
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Heat-Shock Proteins - genetics
Humanities and Social Sciences
Humans
Life Sciences
Loci
Longevity
Longevity - genetics
Meta-analysis
multidisciplinary
Phenotypes
Science
Survival
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Title A meta-analysis of genome-wide association studies identifies multiple longevity genes
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