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

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  • Katherine A. Kentistou
  • Krista Fischer
  • Edith Hofer
  • David W. Clark
  • Teresa Nutile
  • Catriona L. K. Barnes
  • Paul R. H. J. Timmers
  • Ilaria Gandin
  • Aaron F. Mcdaid
  • Thomas Folkmann Hansen
  • Scott D. Gordon
  • Franco Giulianini
  • Abdel Abdellaoui
  • Wei Zhao
  • Carolina Medina-gomez
  • Traci M. Bartz
  • Stella Trompet
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  • Ashley Van Der Spek
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  • Lisa R. Yanek
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  • Ilkka Seppälä
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  • Yasaman Saba
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  • Elisabeth Steinhagen-thiessen
  • Frank J. A. Van Rooij
  • André L. Verbeek
  • Sita H. Vermeulen
  • Peter Vollenweider
  • Yunpeng Wang
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  • Nora Franceschini
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  • Andres Metspalu
  • Dorret I. Boomsma
  • Daniel Chasman
  • Nicholas G. Martin
  • Naveed Sattar
  • Tōnu Esko
  • Zoltán Kutalik

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http://www.nature.com/articles/s41467-017-00934-5
Original languageEnglish
Number of pages13
JournalNature Communications
Volume8
Issue number1
Early online date13 Oct 2017
DOIs
Publication statusE-pub ahead of print - 13 Oct 2017

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 HDL cholesterol levels are most positively genetically correlated with lifespan whilst 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 whilst 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 whilst one year of education adds 11 months to expected lifespan.

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