TY - JOUR

T1 - Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

AU - Joshi, Peter K

AU - Pirastu, Nicola

AU - Kentistou, Katherine A

AU - Fischer, Krista

AU - Hofer, Edith

AU - Schraut, Katharina E

AU - Clark, David W

AU - Nutile, Teresa

AU - Barnes, Catriona L K

AU - Timmers, Paul R H J

AU - Shen, Xia

AU - Gandin, Ilaria

AU - McDaid, Aaron F

AU - Hansen, Thomas Folkmann

AU - Gordon, Scott D

AU - Giulianini, Franco

AU - Boutin, Thibaud S

AU - Abdellaoui, Abdel

AU - Zhao, Wei

AU - Medina-Gomez, Carolina

AU - Bartz, Traci M

AU - Trompet, Stella

AU - Lange, Leslie A

AU - Raffield, Laura

AU - van der Spek, Ashley

AU - Galesloot, Tessel E

AU - Proitsi, Petroula

AU - Yanek, Lisa R

AU - Bielak, Lawrence F

AU - Payton, Antony

AU - Murgia, Federico

AU - Concas, Maria Pina

AU - Biino, Ginevra

AU - Tajuddin, Salman M

AU - Seppälä, Ilkka

AU - Amin, Najaf

AU - Boerwinkle, Eric

AU - Børglum, Anders D

AU - Campbell, Archie

AU - Demerath, Ellen W

AU - Demuth, Ilja

AU - Faul, Jessica D

AU - Ford, Ian

AU - Gialluisi, Alessandro

AU - Gögele, Martin

AU - Graff, MariaElisa

AU - Hingorani, Aroon

AU - Hottenga, Jouke-Jan

AU - Hougaard, David M

AU - Werge, Thomas

AU - Esko, Tõnu

AU - Kutalik, Zoltan

AU - Wilson, James F

AU - et al.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Alleles

KW - Body Mass Index

KW - Coronary Disease/blood

KW - Education

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - HLA-DQ alpha-Chains/genetics

KW - HLA-DRB1 Chains/genetics

KW - Humans

KW - Insulin Resistance/genetics

KW - Life Style

KW - Lipoprotein(a)/genetics

KW - Lipoproteins, HDL/blood

KW - Longevity/genetics

KW - Lung Neoplasms/blood

KW - Obesity/complications

KW - Polymorphism, Single Nucleotide

KW - Smoking/adverse effects

KW - Socioeconomic Factors

U2 - 10.1038/s41467-017-00934-5

DO - 10.1038/s41467-017-00934-5

M3 - Journal article

C2 - 29030599

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 910

ER -