Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Gail DaviesMax LamSarah E HarrisJoey W TrampushMichelle LucianoW David HillSaskia P HagenaarsStuart J RitchieRiccardo E MarioniChloe Fawns-RitchieDavid C M LiewaldJudith A OkelyAri V Ahola-OlliCatriona L K BarnesLars BertramJoshua C BisKatherine E BurdickAndrea ChristoforouPamela DeRosseSrdjan DjurovicThomas EspesethStella GiakoumakiSudheer GiddaluruDaniel E GustavsonCaroline HaywardEdith HoferMohammad Arfan IkramRobert KarlssonEmma KnowlesJari M T LahtiMarkus LeberShuo LiKaren A MatherIngrid MelleDerek W MorrisChristopher OldmeadowTeemu PalviainenAntony PaytonRaha PazokiKatja PetrovicChandra A ReynoldsMuralidharan SargurupremrajMarkus ScholzJennifer A SmithAlbert V SmithNatalie TerzikhanAnbupalam ThalamuthuStella TrompetSven J Van der LeeErin B WareB Gwen WindhamMargaret J WrightJingyun YangJin YuDavid AmesNajaf AminPhillippe AmouyelOle Andreas AndreassenNicola J ArmstrongAmelia A AssarehJohn Richard AttiaDeborah AttixDimitrios AvramopoulosDavid A BennettAnne C BöhmerPatricia A BoyleHenry BrodatyHarry CampbellTyrone D CannonElizabeth T CirulliEliza CongdonEmily Drabant ConleyJanie CorleySimon R CoxAnders M DaleAbbas DehghanDanielle DickDwight DickinsonJohan G ErikssonEvangelos EvangelouJessica D FaulIan FordNelson A FreimerHe GaoIna GieglingNathan A GillespieScott D GordonRebecca F GottesmanMichael E GriswoldVilmundur GudnasonTamara B HarrisAnnette M HartmannAlex HatzimanolisGerardo HeissElizabeth G HollidayPeter K JoshiMika KähönenSharon L R KardiaIda KarlssonLuca KleineidamDavid S KnopmanNicole A KochanBettina KonteJohn B KwokStephanie Le HellardTeresa LeeTerho LehtimäkiShu-Chen LiChristina M LillTian LiuMarisa KoiniEdythe LondonWill T LongstrethOscar L LopezAnu LoukolaTobias LuckAstri Johansen LundervoldAnders LundquistLeo-Pekka LyytikainenNicholas G MartinGrant W MontgomeryAlison D MurrayAnna C NeedRaymond NoordamLars NybergWilliam OllierGoran PapenbergAlison PattieOzren PolasekRussell A PoldrackBruce M PsatySimone ReppermundSteffi G Riedel-HellerRichard J RoseJerome I RotterPanos RoussosSuvi P RovioYasaman SabaFred W SabbPerminder Singh SachdevClaudia L SatizabalMatthias SchmidRodney J ScottMatthew A ScultJeannette SiminoP Eline SlagboomNikolaos SmyrnisAïcha SoumaréNikos C StefanisDavid J StottRichard E StraubKjetil SundetAdele M TaylorKent D TaylorJoanna TzoulakiChristophe TzourioAndré UitterlindenVeronique VitartAristotle N VoineskosJaakko A KaprioMichael WagnerHolger WagnerLeonie WeinholdK Hoyan WenElisabeth WidenQiong YangWei ZhaoHieab H H AdamsDan E ArkingRobert M BilderPanos BitsiosEric BoerwinkleOrnit Chiba-FalekAiden CorvinPhilip Lawrence De JagerStéphanie DebetteGary DonohoePaul ElliottAnnette L FitzpatrickMichael GillDavid C GlahnSara HäggNarelle K HansellAhmad R HaririM Kamran IkramJohan Wouter JukemaEero VuoksimaaMatthew C KellerWilliam S KremenLenore LaunerUlman LindenbergerAarno PalotieNancy L PedersenNeil PendletonDavid J PorteousKatri RäikkönenOlli T RaitakariAlfredo RamirezIvar ReinvangIgor Rudannull Dan RujescuReinhold SchmidtHelena SchmidtPeter W SchofieldPeter R SchofieldJohn M StarrVidar M SteenJulian N TrollorSteven T TurnerCornelia M Van DuijnArno VillringerDaniel R WeinbergerDavid R WeirJames F WilsonAnil MalhotraAndrew M McIntoshCatharine R GaleSudha SeshadriThomas H MosleyJan BresslerTodd LenczIan J DearyPublished in: Nature communications (2018)
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Keyphrases
- genome wide
- dna methylation
- copy number
- healthcare
- blood pressure
- poor prognosis
- public health
- metabolic syndrome
- adipose tissue
- type diabetes
- endothelial cells
- gene expression
- machine learning
- skeletal muscle
- physical activity
- transcription factor
- functional connectivity
- brain injury
- genome wide association study
- blood brain barrier
- arterial hypertension
- weight loss
- health promotion