Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.
Aysu OkbayBart M L BaselmansJan-Emmanuel De NevePatrick TurleyMichel G NivardMark Alan FontanaS Fleur W MeddensRichard Karlsson LinnérCornelius A RietveldJaime DerringerJacob GrattenJames J LeeJimmy Z LiuRonald de VlamingTarunveer S AhluwaliaJadwiga BuchwaldAlana CavadinoAlexis C Frazier-WoodNicholas A FurlotteVictoria GarfieldMarie Henrike GeiselJuan R GonzalezSaskia HaitjemaRobert KarlssonSander W van der LaanKarl-Heinz LadwigJari LahtiSven J Van der LeePenelope A LindTian LiuLindsay MattesonEvelin MihailovMichael B MillerCamelia C MinicaIlja M NolteDennis Mook-KanamoriPeter J van der MostChristopher OldmeadowYong QianOlli RaitakariRajesh RawalAnu RealoRico RueediBörge SchmidtAlbert Vernon SmithEvie StergiakouliToshiko TanakaKent TaylorGudmar ThorleifssonJuho WedenojaJuergen WellmannHarm-Jan WestraSara M WillemsWei Zhaonull nullNajaf AminAndrew BakshiSven BergmannGyda BjornsdottirPatricia A BoyleSamantha CherneySimon R CoxGail DaviesOliver S P DavisJun DingNese DirekPeter EibichRebecca T EmenyGhazaleh FatemifarJessica D FaulLuigi FerrucciAndreas J ForstnerChristian GiegerRicha GuptaTamara B HarrisJuliette M HarrisElizabeth G HollidayJouke-Jan HottengaPhilip L De JagerMarika A KaakinenEero KajantieVille KarhunenIvana KolcicMeena KumariLenore J LaunerLude H FrankeRuifang Li-GaoDavid C LiewaldMarisa KoiniAnu LoukolaPedro Marques-VidalGrant W MontgomeryMiriam A MosingLavinia PaternosterAlison PattieKatja E PetrovicLaura Pulkki-RåbackLydia QuayeKatri RäikkönenIgor RudanRodney J ScottJennifer A SmithAngelina R SutinMaciej TrzaskowskiAnna E VinkhuyzenLei YuDelilah ZabanehJohn Richard AttiaDavid A BennettKlaus BergerLars BertramDorret I BoomsmaHarold SniederShun-Chiao ChangFrancesco CuccaIan J DearyCornelia M van DuijnJohan G ErikssonUte BültmannEco J C N de GeusPatrick J F GroenenVilmundur GudnasonTorben HansenCatharine A HartmanClaire M A HaworthCaroline HaywardAndrew C HeathDavid A HindsElina HyppönenWilliam G IaconoMarjo-Riitta JärvelinKarl-Heinz JöckelJaakko A KaprioSharon L R KardiaLiisa Keltikangas-JärvinenPeter KraftLaura D KubzanskyTerho LehtimäkiPatrik K E MagnussonNicholas G MartinMatt McGueAndres MetspaluMelinda MillsRenée de MutsertAlbertine J OldehinkelGerard PasterkampNancy L PedersenRobert PlominOzren PolasekChristine PowerStephen S RichFrits R RosendaalHester M den RuijterDavid SchlessingerHelena SchmidtRauli SventoReinhold SchmidtBehrooz Z AlizadehThorkild I A SørensenTim D SpectorJohn M StarrKari StefanssonAndrew SteptoeAntonio TerraccianoUnnur ThorsteinsdottirA Roy ThurikNicholas J TimpsonHenning TiemeierAndré G UitterlindenPeter VollenweiderGert G WagnerDavid R WeirJian YangDalton C ConleyGeorge Davey SmithAlbert HofmanMagnus JohannessonDavid I LaibsonSarah E MedlandMichelle N MeyerJoseph K PickrellTõnu EskoRobert F KruegerJonathan P BeauchampPhilipp D KoellingerDaniel J BenjaminMeike BartelsDavid CesariniPublished in: Nature genetics (2016)
Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.