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

TitleGenome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.
Publication TypeJournal Article
Year of Publication2017
AuthorsJoshi PK, Pirastu N, Kentistou KA, et al.
Secondary AuthorsWilson JF
JournalNat Commun
Volume8
Issue1
Pagination910
Date Published2017 10 13
ISSN2041-1723
KeywordsAlleles, Body Mass Index, Coronary Disease, Education, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Insulin Resistance, Life Style, Lipoprotein(a), Lipoproteins, HDL, Longevity, Lung Neoplasms, Obesity, Polymorphism, Single Nucleotide, Smoking, Socioeconomic Factors
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.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

DOI10.1038/s41467-017-00934-5
Alternate JournalNat Commun
PubMed ID29030599
PubMed Central IDPMC5715013
Grant ListMC_PC_14126 / MRC_ / Medical Research Council / United Kingdom
G0900753 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12019/1 / MRC_ / Medical Research Council / United Kingdom
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
MR/K002279/1 / MRC_ / Medical Research Council / United Kingdom
/ WT_ / Wellcome Trust / United Kingdom
G0600237 / MRC_ / Medical Research Council / United Kingdom
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
U01 HL130114 / HL / NHLBI NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
MR/N005813/1 / MRC_ / Medical Research Council / United Kingdom
MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom
UM1 CA182913 / CA / NCI NIH HHS / United States
G0100594 / MRC_ / Medical Research Council / United Kingdom
U54 GM115428 / GM / NIGMS NIH HHS / United States
BB/F022441/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
G0901461 / MRC_ / Medical Research Council / United Kingdom