Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.
Peter K JoshiNicola PirastuKatherine A KentistouKrista FischerEdith HoferKatharina E SchrautDavid W ClarkTeresa NutileCatriona L K BarnesPaul R H J TimmersXia ShenIlaria GandinAaron F McDaidThomas Folkmann HansenScott D GordonFranco GiulianiniThibaud S BoutinAbdel AbdellaouiWei ZhaoCarolina Medina-GomezTraci M BartzStella TrompetLeslie A LangeLaura RaffieldAshley van der SpekTessel E GaleslootPetroula ProitsiLisa R YanekLawrence F BielakAntony PaytonFederico MurgiaMaria Pina ConcasGinevra BiinoSalman M TajuddinIlkka SeppäläNajaf AminEric BoerwinkleAnders D BørglumArchie CampbellEllen W DemerathIlja DemuthJessica D FaulIan FordAlessandro GialluisiMartin GögeleMariaElisa GraffAroon HingoraniJouke-Jan HottengaDavid Michael HougaardMikko A HurmeMohammad Arfan IkramMarja JylhäDiana KuhLannie LigthartChristina M LillUlman LindenbergerThomas LumleyReedik MägiPedro-Manuel Marques-VidalSarah E MedlandLili A MilaniReka NagyWilliam E R OllierPatricia A PeyserPeter P PramstallerPaul M RidkerFernando RivadeneiraDaniela RuggieroYasaman SabaReinhold SchmidtHelena SchmidtP Eline SlagboomBlair Hamilton SmithJennifer A SmithNona SotoodehniaElisabeth Steinhagen-ThiessenFrank J A van RooijAndré L VerbeekSita H VermeulenPeter VollenweiderYunpeng WangThomas WergeJohn B WhitfieldAlan B ZondermanTerho LehtimäkiMichele K EvansMario PirastuChristian FuchsbergerLars BertramNeil PendletonSharon L R KardiaMarina CiulloDiane M BeckerAndrew WongBruce M PsatyCornelia M van DuijnJames G WilsonJohan Wouter JukemaLambertus KiemeneyAndré G UitterlindenNora FranceschiniKari E NorthDavid R WeirAndres MetspaluDorret I BoomsmaCaroline HaywardDaniel ChasmanNicholas G MartinNaveed SattarHarry CampbellTōnu EskoZoltán KutalikJames F WilsonPublished in: 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.
Keyphrases
- coronary artery disease
- endothelial cells
- body mass index
- insulin resistance
- genome wide
- systematic review
- metabolic syndrome
- high density
- induced pluripotent stem cells
- healthcare
- smoking cessation
- drosophila melanogaster
- weight loss
- weight gain
- high fat diet
- physical activity
- pluripotent stem cells
- cardiovascular disease
- heart failure
- transcription factor
- skeletal muscle
- coronary artery bypass grafting
- acute coronary syndrome
- gene expression
- cognitive decline
- meta analyses
- machine learning
- climate change
- high fat diet induced
- deep learning
- glycemic control
- data analysis