Meta-Analysis

. 2019 Aug 14;10(1):3669.

doi: 10.1038/s41467-019-11558-2.

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

Joris Deelen^{1

2}, Daniel S Evans³, Dan E Arking⁴, Niccolò Tesi^{5

6

7}, Marianne Nygaard⁸, Xiaomin Liu^{9

10}, Mary K Wojczynski¹¹, Mary L Biggs^{12

13}, Ashley van der Spek¹⁴, Gil Atzmon^{15

16}, Erin B Ware¹⁷, Chloé Sarnowski¹⁸, Albert V Smith^{19

20}, Ilkka Seppälä²¹, Heather J Cordell²², Janina Dose²³, Najaf Amin¹⁴, Alice M Arnold¹², Kristin L Ayers²⁴, Nir Barzilai¹⁶, Elizabeth J Becker²⁵, Marian Beekman²⁶, Hélène Blanché²⁷, Kaare Christensen^{8

28

29}, Lene Christiansen^{8

30}, Joanna C Collerton³¹, Sarah Cubaynes³², Steven R Cummings³³, Karen Davies³⁴, Birgit Debrabant³⁵, Jean-François Deleuze^{27

36}, Rachel Duncan^{31

37}, Jessica D Faul¹⁷, Claudio Franceschi^{38

39}, Pilar Galan⁴⁰, Vilmundur Gudnason^{20

41}, Tamara B Harris⁴², Martijn Huisman^{43

44}, Mikko A Hurme⁴⁵, Carol Jagger^{31

37}, Iris Jansen^{5

46}, Marja Jylhä⁴⁷, Mika Kähönen⁴⁸, David Karasik^{49

50}, Sharon L R Kardia⁵¹, Andrew Kingston^{31

37}, Thomas B L Kirkwood³⁷, Lenore J Launer⁴², Terho Lehtimäki²¹, Wolfgang Lieb⁵², Leo-Pekka Lyytikäinen²¹, Carmen Martin-Ruiz³⁴, Junxia Min⁵³, Almut Nebel²³, Anne B Newman⁵⁴, Chao Nie⁹, Ellen A Nohr⁵⁵, Eric S Orwoll⁵⁶, Thomas T Perls⁵⁷, Michael A Province¹¹, Bruce M Psaty^{13

58

59

60}, Olli T Raitakari^{61

62}, Marcel J T Reinders⁷, Jean-Marie Robine^{32

63}, Jerome I Rotter^{64

65}, Paola Sebastiani¹⁸, Jennifer Smith^{17

51}, Thorkild I A Sørensen^{66

67}, Kent D Taylor^{64

68}, André G Uitterlinden^{14

69}, Wiesje van der Flier^{5

43}, Sven J van der Lee^{5

6}, Cornelia M van Duijn^{14

70}, Diana van Heemst⁷¹, James W Vaupel⁷², David Weir¹⁷, Kenny Ye⁷³, Yi Zeng^{74

75}, Wanlin Zheng³³, Henne Holstege^{5

6

7}, Douglas P Kiel^{50

76

77}, Kathryn L Lunetta¹⁸, P Eline Slagboom⁷⁸, Joanne M Murabito^{79

80}

Affiliations

¹ Max Planck Institute for Biology of Ageing, 50866, Cologne, Germany. Joris.Deelen@age.mpg.de.
² Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. Joris.Deelen@age.mpg.de.
³ California Pacific Medical Center Research Institute, San Francisco, CA, 94158, USA. DEvans@sfcc-cpmc.net.
⁴ McKusick-Nathans Institute of Genetic Medicine, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁵ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1007 MB, Amsterdam, The Netherlands.
⁶ Department of Clinical Genetics, Amsterdam UMC, 1007 MB, Amsterdam, The Netherlands.
⁷ Delft Bioinformatics Lab, Delft University of Technology, 2600 GA, Delft, The Netherlands.
⁸ The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, 5000, Odense C, Denmark.
⁹ BGI-Shenzhen, Shenzhen, 518083, China.
¹⁰ China National Genebank, BGI-Shenzhen, Shenzhen, 518120, China.
¹¹ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
¹² Department of Biostatistics, University of Washington, Seattle, WA, 98115, USA.
¹³ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
¹⁴ Department of Epidemiology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
¹⁵ Department of Biology, Faculty of Natural Science, University of Haifa, Haifa, 3498838, Israel.
¹⁶ Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
¹⁷ Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, 48104, USA.
¹⁸ Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
¹⁹ School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
²⁰ Icelandic Heart Association, 201, Kópavogur, Iceland.
²¹ Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
²² Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
²³ Institute of Clinical Molecular Biology, Kiel University, 24105, Kiel, Germany.
²⁴ Sema4, a Mount Sinai venture, Stamford, CT, 06902, USA.
²⁵ Bioinformatics Program, Boston University, Boston, MA, 02118, USA.
²⁶ Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
²⁷ Fondation Jean Dausset-CEPH, 75010, Paris, France.
²⁸ Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000, Odense C, Denmark.
²⁹ Department of Clinical Genetics, Odense University Hospital, 5000, Odense C, Denmark.
³⁰ Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.
³¹ Institute of Health & Society, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
³² MMDN, Univ. Montpellier, EPHE, Unité Inserm 1198, PSL Research University, 34095, Montpellier, France.
³³ California Pacific Medical Center Research Institute, San Francisco, CA, 94158, USA.
³⁴ Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
³⁵ Department of Public Health, University of Southern Denmark, 5000, Odense C, Denmark.
³⁶ Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie François Jacob, 91000, Evry, France.
³⁷ Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
³⁸ Department of Applied Mathematics and Centre of Bioinformatics, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia.
³⁹ IRCCS Institute of Neurological Sciences of Bologna (ISNB), 40124, Bologna, Italy.
⁴⁰ EREN, UMR U1153 Inserm/U1125 Inra/Cnam/Paris 13, Université Paris 13, CRESS, 93017, Bobigny, France.
⁴¹ Faculty of Medicine, University of Iceland, 101, Reykjavik, Iceland.
⁴² Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD, 20892, USA.
⁴³ Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1007 MB, Amsterdam, The Netherlands.
⁴⁴ Amsterdam Public Health Research Institute, 1007 MB, Amsterdam, The Netherlands.
⁴⁵ Department of Microbiology and Immunology, Faculty of Medicine and Health Technology, Tampere University, 33014, Tampere, Finland.
⁴⁶ Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, The Netherlands.
⁴⁷ Faculty of Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), Tampere University, 33104, Tampere, Finland.
⁴⁸ Department of Clinical Physiology, Tampere University Hospital and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, 33521, Tampere, Finland.
⁴⁹ Azrieli Faculty of Medicine, Bar Ilan University, Safed, 13010, Israel.
⁵⁰ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA.
⁵¹ School of Public Health, Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵² Institute of Epidemiology and Biobank PopGen, Kiel University, 24105, Kiel, Germany.
⁵³ Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, 311058, China.
⁵⁴ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
⁵⁵ Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, 5000, Odense C, Denmark.
⁵⁶ Bone and Mineral Unit, Oregon Health Sciences University, Portland, OR, 97239, USA.
⁵⁷ Department of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, 02118, USA.
⁵⁸ Department of Epidemiology, University of Washington, Seattle, WA, 98101, USA.
⁵⁹ Department of Health Services, University of Washington, Seattle, WA, 98101, USA.
⁶⁰ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
⁶¹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland.
⁶² Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20014, Turku, Finland.
⁶³ CERMES3, UMR CNRS 8211-Unité Inserm 988-EHESS-Université Paris Descartes, 94801, Paris, France.
⁶⁴ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁶⁵ Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁶⁶ 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, 2200, Copenhagen N, Denmark.
⁶⁷ MRC Integrative Epidemiology Unit, Bristol University, BS8 2BN, Bristol, UK.
⁶⁸ Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁶⁹ Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
⁷⁰ Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
⁷¹ Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
⁷² Max Planck Institute for Demographic Research, 18057, Rostock, Germany.
⁷³ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
⁷⁴ Center for Healthy Aging and Development Studies, National School of Development and Raissun Institute for Advanced Studies, Peking University, 100871, Beijing, China.
⁷⁵ Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC, 27710, USA.
⁷⁶ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.
⁷⁷ Broad Institute of MIT & Harvard, Cambridge, MA, 02142, USA.
⁷⁸ Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. P.Slagboom@lumc.nl.
⁷⁹ NHLBI's and Boston University's Framingham Heart Study, Framingham, MA, 01702, USA. murabito@bu.edu.
⁸⁰ Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA. murabito@bu.edu.

PMID: 31413261
PMCID: PMC6694136
DOI: 10.1038/s41467-019-11558-2

Meta-Analysis

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

Joris Deelen et al. Nat Commun. 2019.

. 2019 Aug 14;10(1):3669.

doi: 10.1038/s41467-019-11558-2.

Authors

Affiliations

¹ Max Planck Institute for Biology of Ageing, 50866, Cologne, Germany. Joris.Deelen@age.mpg.de.
² Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. Joris.Deelen@age.mpg.de.
³ California Pacific Medical Center Research Institute, San Francisco, CA, 94158, USA. DEvans@sfcc-cpmc.net.
⁴ McKusick-Nathans Institute of Genetic Medicine, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁵ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1007 MB, Amsterdam, The Netherlands.
⁶ Department of Clinical Genetics, Amsterdam UMC, 1007 MB, Amsterdam, The Netherlands.
⁷ Delft Bioinformatics Lab, Delft University of Technology, 2600 GA, Delft, The Netherlands.
⁸ The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, 5000, Odense C, Denmark.
⁹ BGI-Shenzhen, Shenzhen, 518083, China.
¹⁰ China National Genebank, BGI-Shenzhen, Shenzhen, 518120, China.
¹¹ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
¹² Department of Biostatistics, University of Washington, Seattle, WA, 98115, USA.
¹³ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
¹⁴ Department of Epidemiology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
¹⁵ Department of Biology, Faculty of Natural Science, University of Haifa, Haifa, 3498838, Israel.
¹⁶ Departments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
¹⁷ Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, 48104, USA.
¹⁸ Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
¹⁹ School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
²⁰ Icelandic Heart Association, 201, Kópavogur, Iceland.
²¹ Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
²² Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
²³ Institute of Clinical Molecular Biology, Kiel University, 24105, Kiel, Germany.
²⁴ Sema4, a Mount Sinai venture, Stamford, CT, 06902, USA.
²⁵ Bioinformatics Program, Boston University, Boston, MA, 02118, USA.
²⁶ Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
²⁷ Fondation Jean Dausset-CEPH, 75010, Paris, France.
²⁸ Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000, Odense C, Denmark.
²⁹ Department of Clinical Genetics, Odense University Hospital, 5000, Odense C, Denmark.
³⁰ Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.
³¹ Institute of Health & Society, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
³² MMDN, Univ. Montpellier, EPHE, Unité Inserm 1198, PSL Research University, 34095, Montpellier, France.
³³ California Pacific Medical Center Research Institute, San Francisco, CA, 94158, USA.
³⁴ Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
³⁵ Department of Public Health, University of Southern Denmark, 5000, Odense C, Denmark.
³⁶ Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie François Jacob, 91000, Evry, France.
³⁷ Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
³⁸ Department of Applied Mathematics and Centre of Bioinformatics, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, 603022, Russia.
³⁹ IRCCS Institute of Neurological Sciences of Bologna (ISNB), 40124, Bologna, Italy.
⁴⁰ EREN, UMR U1153 Inserm/U1125 Inra/Cnam/Paris 13, Université Paris 13, CRESS, 93017, Bobigny, France.
⁴¹ Faculty of Medicine, University of Iceland, 101, Reykjavik, Iceland.
⁴² Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD, 20892, USA.
⁴³ Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1007 MB, Amsterdam, The Netherlands.
⁴⁴ Amsterdam Public Health Research Institute, 1007 MB, Amsterdam, The Netherlands.
⁴⁵ Department of Microbiology and Immunology, Faculty of Medicine and Health Technology, Tampere University, 33014, Tampere, Finland.
⁴⁶ Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, The Netherlands.
⁴⁷ Faculty of Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), Tampere University, 33104, Tampere, Finland.
⁴⁸ Department of Clinical Physiology, Tampere University Hospital and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, 33521, Tampere, Finland.
⁴⁹ Azrieli Faculty of Medicine, Bar Ilan University, Safed, 13010, Israel.
⁵⁰ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA.
⁵¹ School of Public Health, Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁵² Institute of Epidemiology and Biobank PopGen, Kiel University, 24105, Kiel, Germany.
⁵³ Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, 311058, China.
⁵⁴ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
⁵⁵ Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, 5000, Odense C, Denmark.
⁵⁶ Bone and Mineral Unit, Oregon Health Sciences University, Portland, OR, 97239, USA.
⁵⁷ Department of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, 02118, USA.
⁵⁸ Department of Epidemiology, University of Washington, Seattle, WA, 98101, USA.
⁵⁹ Department of Health Services, University of Washington, Seattle, WA, 98101, USA.
⁶⁰ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
⁶¹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland.
⁶² Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20014, Turku, Finland.
⁶³ CERMES3, UMR CNRS 8211-Unité Inserm 988-EHESS-Université Paris Descartes, 94801, Paris, France.
⁶⁴ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁶⁵ Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁶⁶ 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, 2200, Copenhagen N, Denmark.
⁶⁷ MRC Integrative Epidemiology Unit, Bristol University, BS8 2BN, Bristol, UK.
⁶⁸ Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁶⁹ Department of Internal Medicine, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
⁷⁰ Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
⁷¹ Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
⁷² Max Planck Institute for Demographic Research, 18057, Rostock, Germany.
⁷³ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
⁷⁴ Center for Healthy Aging and Development Studies, National School of Development and Raissun Institute for Advanced Studies, Peking University, 100871, Beijing, China.
⁷⁵ Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC, 27710, USA.
⁷⁶ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.
⁷⁷ Broad Institute of MIT & Harvard, Cambridge, MA, 02142, USA.
⁷⁸ Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. P.Slagboom@lumc.nl.
⁷⁹ NHLBI's and Boston University's Framingham Heart Study, Framingham, MA, 01702, USA. murabito@bu.edu.
⁸⁰ Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA. murabito@bu.edu.

PMID: 31413261
PMCID: PMC6694136
DOI: 10.1038/s41467-019-11558-2

Erratum in

Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes.
Deelen J, Evans DS, Arking DE, Tesi N, Nygaard M, Liu X, Wojczynski MK, Biggs ML, van der Spek A, Atzmon G, Ware EB, Sarnowski C, Smith AV, Seppälä I, Cordell HJ, Dose J, Amin N, Arnold AM, Ayers KL, Barzilai N, Becker EJ, Beekman M, Blanché H, Christensen K, Christiansen L, Collerton JC, Cubaynes S, Cummings SR, Davies K, Debrabant B, Deleuze JF, Duncan R, Faul JD, Franceschi C, Galan P, Gudnason V, Harris TB, Huisman M, Hurme MA, Jagger C, Jansen I, Jylhä M, Kähönen M, Karasik D, Kardia SLR, Kingston A, Kirkwood TBL, Launer LJ, Lehtimäki T, Lieb W, Lyytikäinen LP, Martin-Ruiz C, Min J, Nebel A, Newman AB, Nie C, Nohr EA, Orwoll ES, Perls TT, Province MA, Psaty BM, Raitakari OT, Reinders MJT, Robine JM, Rotter JI, Sebastiani P, Smith J, Sørensen TIA, Taylor KD, Uitterlinden AG, van der Flier W, van der Lee SJ, van Duijn CM, van Heemst D, Vaupel JW, Weir D, Ye K, Zeng Y, Zheng W, Holstege H, Kiel DP, Lunetta KL, Slagboom PE, Murabito JM. Deelen J, et al. Nat Commun. 2021 Apr 23;12(1):2463. doi: 10.1038/s41467-021-22613-2. Nat Commun. 2021. PMID: 33893282 Free PMC article. No abstract available.

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Results of the European genome-wide association meta-analyses. Manhattan plot presenting the –log₁₀ P-values from the European genome-wide association meta-analysis of the 90th percentile cases versus all controls (a) and 99th percentile cases versus all controls (b). The red line indicates the threshold for genome-wide significance (P ≤ 5 × 10⁻⁸), while the blue line indicates the threshold for genetic variants that showed a suggestive significant association (P ≤ 1 × 10⁻⁶). The variants that are reported in Table 2 are highlighted in green. For representation purposes, the maximum of the y-axis was set to 14. Regional association plot for the *APOE* (c) and *GPR78* (d) loci based on the results from the 90th percentile cases versus all controls meta-analysis. The colour of the variants is based on the linkage disequilibrium with rs429358 (ApoE ε4) (c) or rs7676745 (d)

**Fig. 2**
Study-specific results for the genetic variants in *APOE* and *GPR78*. Forest plots for the ApoE ε4 (a) and ε2 (b) variants and rs7676745 (c) based on the results from the 90th percentile versus all controls analysis. The size of the boxes represents the sample size of the cohort. We had no data available for ApoE ε4 in LLFS and for rs7676745 in DKLS, GEHA Italy, GEHA Danish, LLS (combined with GEHA Dutch), Longevity, and Newcastle 85 + . The data for ApoE ε2 in FHS was based on imputation using the Haplotype Reference Consortium reference panel due to the low-imputation quality of this variant when using the 1000 Genomes reference panel

**Fig. 3**
Results of the trans-ethnic genome-wide association meta-analyses. Manhattan plot presenting the –log₁₀ P-values from the trans-ethnic genome-wide association meta-analysis of the 90th percentile cases versus all controls (a) and 99th percentile cases versus all controls (b). The red line indicates the threshold for genome-wide significance (P ≤ 5 × 10⁻⁸), while the blue line indicates the threshold for genetic variants that showed a suggestive significant association (P ≤ 1 × 10⁻⁶)

See this image and copyright information in PMC

References

1. Oeppen J, Vaupel JW. Demography. Broken limits life Expect. Sci. 2002;296:1029–1031. - PubMed
1. van den Berg N, Beekman M, Smith KR, Janssens A, Slagboom PE. Historical demography and longevity genetics: back to the future. Ageing Res. Rev. 2017;38:28–39. doi: 10.1016/j.arr.2017.06.005. - DOI - PubMed
1. Kaplanis J, et al. Quantitative analysis of population-scale family trees with millions of relatives. Science. 2018;360:171–175. doi: 10.1126/science.aam9309. - DOI - PMC - PubMed
1. Ruby JG, et al. Estimates of the heritability of human longevity are substantially inflated due to assortative mating. Genetics. 2018;210:1109–1124. doi: 10.1534/genetics.118.301613. - DOI - PMC - PubMed
1. Sebastiani P, Nussbaum L, Andersen SL, Black MJ, Perls TT. Increasing sibling relative risk of survival to older and older ages and the importance of precise definitions of “aging,” “life span,” and “longevity”. J. Gerontol. A Biol. Sci. Med. Sci. 2016;71:340–346. doi: 10.1093/gerona/glv020. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- H1 Connect - Access expert opinions and insights on biomedical research.
Molecular Biology Databases
- GlyGen glycoinformatics resource
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Miscellaneous