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Cited by 161Genetic Associations and EpidemiologyGenetics, Aging, and Longevity in Model OrganismsGenetics and Physical Performance

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

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Joshi, Peter K., Pirastu, Nicola, Kentistou, Katherine A., Fischer, Krista, Hofer, Edith, Schraut, Katharina E., Clark, David W., Nutile, Teresa +105 more·2017·Nature Communications
DOI 10.1038/s41467-017-00934-5PMC PMC5715013
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Abstract

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents’ survival, we discover two regions associated with longevity ( HLA-DQA1/DRB1 and LPA ). We also validate previous suggestions that APOE , CHRNA3/5 , CDKN2A/B , SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.

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  • Several studies of large populations of individuals from European ancestry have raised the possibility that APOE is a longevity gene, with the APOEε2 variant associated with longer survival and the APOEε4 with shorter survival in a dose-dependent manner.

    “Several studies of large populations of individuals from European ancestry have raised the possibility that APOE is a longevity gene, with the APOEε2 variant associated with longer survival and the APOEε4 with shorter survival in a dose-dependent manner90–94.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [90]

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Authors
Joshi, P. K., Pirastu, N., Kentistou, K. A., Fischer, K., Hofer, E., Schraut, K. E., Clark, D. W., Nutile, T., Barnes, C. L. K., Timmers, P. R. H. J., Shen, X., Gandin, I., McDaid, A. F., Hansen, T. F., Gordon, S. D., Giulianini, F., Boutin, T. S., Abdellaoui, A., Zhao, W., Medina-Gomez, C., Bartz, T. M., Trompet, S., Lange, L. A., Raffield, L., van der Spek, A., Galesloot, T. E., Proitsi, P., Yanek, L. R., Bielak, L. F., Payton, A., Murgia, F., Concas, M. P., Biino, G., Tajuddin, S. M., Seppälä, I., Amin, N., Boerwinkle, E., Børglum, A. D., Campbell, A., Demerath, E. W., Demuth, I., Faul, J. D., Ford, I., Gialluisi, A., Gögele, M., Graff, M., Hingorani, A., Hottenga, J.-J., Hougaard, D. M., Hurme, M. A., Ikram, M. A., Jylhä, M., Kuh, D., Ligthart, L., Lill, C. M., Lindenberger, U., Lumley, T., Mägi, R., Marques-Vidal, P., Medland, S. E., Milani, L., Nagy, R., Ollier, W. E. R., Peyser, P. A., Pramstaller, P. P., Ridker, P. M., Rivadeneira, F., Ruggiero, D., Saba, Y., Schmidt, R., Schmidt, H., Slagboom, P. E., Smith, B. H., Smith, J. A., Sotoodehnia, N., Steinhagen-Thiessen, E., van Rooij, F. J. A., Verbeek, A. L., Vermeulen, S. H., Vollenweider, P., Wang, Y., Werge, T., Whitfield, J. B., Zonderman, A. B., Lehtimäki, T., Evans, M. K., Pirastu, M., Fuchsberger, C., Bertram, L., Pendleton, N., Kardia, S. L. R., Ciullo, M., Becker, D. M., Wong, A., Psaty, B. M., van Duijn, C. M., Wilson, J. G., Jukema, J. W., Kiemeney, L., Uitterlinden, A. G., Franceschini, N., North, K. E., Weir, D. R., Metspalu, A., Boomsma, D. I., Hayward, C., Chasman, D., Martin, N. G., Sattar, N., Campbell, H., Esko, T., Kutalik, Z., & Wilson, J. F.
Affiliations
  • University of Edinburgh (GB)
  • The Queen's Medical Research Institute (GB)
  • University of Tartu (EE)
  • Medical University of Graz (AT)
  • Institute of Genetics and Biophysics (IT)
  • Karolinska Institutet (SE)
  • University of Trieste (IT)
  • SIB Swiss Institute of Bioinformatics (CH)
  • Sankt Hans Hospital (DK)
  • QIMR Berghofer Medical Research Institute (AU)
  • Brigham and Women's Hospital (US)
  • Western General Hospital (GB)
  • Amsterdam Public Health (NL)
  • University of Michigan (US)
  • University of Washington (US)
  • Leiden University Medical Center (NL)
  • University of Colorado Anschutz (US)
  • University of North Carolina at Chapel Hill (US)
  • Radboud University Medical Center (NL)
  • MRC Unit for Lifelong Health and Ageing (GB)
  • Johns Hopkins University (US)
  • University of Manchester (GB)
  • Eurac Research (IT)
  • Institute of Genetic and Biomedical Research (IT)
  • National Research Council (IT)
  • National Institutes of Health (US)
  • Tampere University (FI)
  • Erasmus MC (NL)
  • The University of Texas Health Science Center at Houston (US)
  • Aarhus University (DK)
  • Institute of Genetics and Cancer (GB)
  • University of Minnesota (US)
  • Charité – Universitätsmedizin Berlin (DE)
  • University of Glasgow (GB)
  • Istituto Neurologico Mediterraneo (IT)
  • University College London (GB)
  • Statens Serum Institut (DK)
  • University of Lübeck (DE)
  • Max Planck Institute for Human Development (DE)
  • University of Auckland (NZ)
  • Centre Hospitalier Universitaire Vaudois (CH)
  • Manchester Academic Health Science Centre (GB)
  • University of Dundee (GB)
  • University of Oslo (NO)
  • Imperial College London (GB)
  • Kaiser Permanente Washington Health Research Institute (US)
Corresponding author
Joshi, Peter K.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-10-13
Volume
8
Issue
1
Pages
910-910
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-00934-5
PMC
PMC5715013
OpenAlex
W2750901335
Cited by
161
References
7
Citations by year
2026: 7 · 2025: 22 · 2024: 15 · 2023: 13 · 2022: 15 · 2021: 18 · 2020: 25 · 2019: 25 · 2018: 19 · 2017: 1 · 2015: 1
FWCI
12.57
Type
journal article
Language
en
Open access
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Funders
  • Wellcome Trust
  • Lundbeckfonden (R155-2014-1724)
  • Tartu Ülikool
  • National Institutes of Health (1r01hl120393-01a1)
  • Medical Research Council (MR/K026992/1, MR/N005813/1, MC_PC_14126, 1805065, MR/K002279/1, 1811434, 1805084)
  • Biotechnology and Biological Sciences Research Council (BB/F022441/1)
  • National Heart, Lung, and Blood Institute (R01-HL120393, U01HL130114, U01HL120393, R01HL105756, T32HL129982)
  • National Cancer Institute (UM1CA182913)
  • National Institute of General Medical Sciences (U54GM115428)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords
human longevity, lifespan, LPA, apolipoprotein E, CDKN2A/B, SH2B3, FOXO3, educational attainment, smoking, body mass index, obesity, coronary artery disease, HDL cholesterol, insulin resistance, lung cancer, genetic correlation, aging
MeSH terms
Alleles, Coronary Disease, Education, Humans, Insulin Resistance, Life Style, Lipoproteins, HDL, Longevity, Lung Neoplasms, Obesity, Smoking, Socioeconomic Factors, Body Mass Index, Lipoprotein(a), Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, HLA-DRB1 Chains, HLA-DQ alpha-Chains

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