A meta-analysis of genome-wide association studies identifies multiple longevity genes.
Joris DeelenDaniel S EvansDan E ArkingNiccolo' TesiMarianne NygaardXiaomin LiuMary K WojczynskiMary L BiggsAshley van der SpekGil AtzmonErin B WareChloé SarnowskiAlbert V SmithIlkka SeppäläHeather J CordellJanina DoseNajaf AminAlice M ArnoldKristin L AyersNir BarzilaiElizabeth J BeckerMarian BeekmanHélène BlanchéKaare ChristensenLene ChristiansenJoanna C CollertonSarah CubaynesSteven R CummingsKaren DaviesBirgit DebrabantJean-François DeleuzeRachel DuncanJessica D FaulClaudio FranceschiPilar GalanVilmundur G GudnasonTamara B HarrisMartijn HuismanMikko A HurmeCarol JaggerIris JansenMarja JylhäMika KähönenDavid KarasikSharon L R KardiaAndrew KingstonThomas B L KirkwoodLenore J LaunerTerho LehtimäkiWolfgang LiebLeo-Pekka LyytikäinenCarmen Martín-RuizJunxia MinAlmut NebelAnne B NewmanChao NieEllen A NohrEric S OrwollThomas T PerlsMichael A ProvinceBruce M PsatyOlli T RaitakariMarcel J T ReindersJean Marie RobineJerome I RotterPaola SebastianiJennifer A SmithThorkild I A SørensenKent D TaylorAndre G UitterlindenWiesje van der FlierSven J Van der LeeCornelia M van DuijnDiana van HeemstJames W VaupelDavid R WeirKenny YeYi ZengWanlin ZhengHenne HolstegeDouglas P KielKathryn L LunettaP Eline SlagboomJoanne M MurabitoPublished in: Nature communications (2019)
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
Keyphrases
- genome wide
- genome wide association
- drosophila melanogaster
- systematic review
- public health
- high fat diet
- case control
- dna methylation
- copy number
- cognitive decline
- poor prognosis
- emergency department
- meta analyses
- type diabetes
- transcription factor
- long non coding rna
- bioinformatics analysis
- drug induced
- health promotion