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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Peter K Joshi
  • Nicola Pirastu
  • Katherine A Kentistou
  • Krista Fischer
  • Edith Hofer
  • Katharina E Schraut
  • David W Clark
  • Teresa Nutile
  • Catriona L K Barnes
  • Paul R H J Timmers
  • Xia Shen
  • Ilaria Gandin
  • Aaron F McDaid
  • Thomas Folkmann Hansen
  • Scott D Gordon
  • Franco Giulianini
  • Thibaud S Boutin
  • Abdel Abdellaoui
  • Wei Zhao
  • Carolina Medina-Gomez
  • Traci M Bartz
  • Stella Trompet
  • Leslie A Lange
  • Laura Raffield
  • Ashley van der Spek
  • Tessel E Galesloot
  • Petroula Proitsi
  • Lisa R Yanek
  • Lawrence F Bielak
  • Antony Payton
  • Federico Murgia
  • Maria Pina Concas
  • Ginevra Biino
  • Salman M Tajuddin
  • Ilkka Seppälä
  • Najaf Amin
  • Eric Boerwinkle
  • Anders D Børglum
  • Archie Campbell
  • Ellen W Demerath
  • Ilja Demuth
  • Jessica D Faul
  • Ian Ford
  • Alessandro Gialluisi
  • Martin Gögele
  • MariaElisa Graff
  • Aroon Hingorani
  • Jouke-Jan Hottenga
  • David M Hougaard
  • Werge, Thomas
  • Tõnu Esko
  • Zoltan Kutalik
  • James F Wilson
  • et al.

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.

Original languageEnglish
Article number910
JournalNature Communications
Volume8
Number of pages13
ISSN2041-1723
DOIs
Publication statusPublished - 2017

    Research areas

  • Alleles, Body Mass Index, Coronary Disease/blood, Education, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, HLA-DQ alpha-Chains/genetics, HLA-DRB1 Chains/genetics, Humans, Insulin Resistance/genetics, Life Style, Lipoprotein(a)/genetics, Lipoproteins, HDL/blood, Longevity/genetics, Lung Neoplasms/blood, Obesity/complications, Polymorphism, Single Nucleotide, Smoking/adverse effects, Socioeconomic Factors

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