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

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 | Mikko A Hurme | M Arfan Ikram | Marja Jylhä | Diana Kuh | Lannie Ligthart | Christina M Lill | Ulman Lindenberger | Thomas Lumley | Reedik Mägi | Pedro Marques-Vidal | Sarah E Medland | Lili Milani | Reka Nagy | William E R Ollier | Patricia A Peyser | Peter P Pramstaller | Paul M Ridker | Fernando Rivadeneira | Daniela Ruggiero | Yasaman Saba | Reinhold Schmidt | Helena Schmidt | P Eline Slagboom | Blair H Smith | Jennifer A Smith | Nona Sotoodehnia | Elisabeth Steinhagen-Thiessen | Frank J A van Rooij | André L Verbeek | Sita H Vermeulen | Peter Vollenweider | Yunpeng Wang | Thomas Werge | John B Whitfield | Alan B Zonderman | Terho Lehtimäki | Michele K Evans | Mario Pirastu | Christian Fuchsberger | Lars Bertram | Neil Pendleton | Sharon L R Kardia | Marina Ciullo | Diane M Becker | Andrew Wong | Bruce M Psaty | Cornelia M van Duijn | James G Wilson | J Wouter Jukema | Lambertus Kiemeney | André G Uitterlinden | Nora Franceschini | Kari E North | David R Weir | Andres Metspalu | Dorret I Boomsma | Caroline Hayward | Daniel Chasman | Nicholas G Martin | Naveed Sattar | Harry Campbell | Tōnu Esko | Zoltán Kutalik | James F Wilson
Nature communications | 2017

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.

Pubmed ID: 29030599 RIS Download

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Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL120393
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/F022441/1
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL130114
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL120393
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL105756
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL129982
  • Agency: Medical Research Council, United Kingdom
    Id: G0100594
  • Agency: Medical Research Council, United Kingdom
    Id: G0901461
  • Agency: NIGMS NIH HHS, United States
    Id: U54 GM115428
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K002279/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12019/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_14126
  • Agency: Medical Research Council, United Kingdom
    Id: MR/N005813/1
  • Agency: Medical Research Council, United Kingdom
    Id: G0600237
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_U127561128
  • Agency: NCI NIH HHS, United States
    Id: UM1 CA182913
  • Agency: Medical Research Council, United Kingdom
    Id: G0900753
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: MC_QA137853
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K026992/1

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METAL (tool)

RRID:SCR_002013

Software application designed to facilitate meta-analysis of large datasets (such as several whole genome scans) in a convenient, rapid and memory efficient manner. (entry from Genetic Analysis Software)

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GWAMA (tool)

RRID:SCR_006624

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software tool for meta analysis of whole genome association data.

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