Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.
Edith HoferGennady V RoshchupkinHieab H H AdamsMaria J KnolHonghuang LinShuo LiHabil ZareShahzad AhmadNicola J ArmstrongClaudia L SatizabalManon BernardJoshua C BisNathan A GillespieMichelle LucianoAniket MishraMarkus ScholzAlexander TeumerRui XiaXueqiu JianThomas H MosleyYasaman SabaLukas PirpamerStephan SeilerJames T BeckerOwen CarmichaelJerome I RotterBruce M PsatyOscar L LopezNajaf AminSven J van der LeeQiong YangJayanadra J HimaliPauline MaillardAlexa S BeiserCharles DeCarliSherif KaramaLindsay LewisMathew A HarrisMark E BastinIan J DearyA Veronica WitteFrauke BeyerMarkus LoefflerKaren A MatherPeter R SchofieldAnbupalam ThalamuthuJohn B KwokMargaret J WrightDavid AmesJulian N TrollorJiyang JiangHenry BrodatyWei WenMeike W VernooijAlbert HofmanAndre G UitterlindenWiro J NiessenKatharina WittfeldRobin BülowLinus VölkerZdenka PausovaGilbert Bruce PikeSophie MaingaultStephanie DebetteChristophe TzourioPhillippe AmouyelBernard MazoyerMichael C NealeCarol E FranzMichael J LyonsMatthew S PanizzonOle Andreas AndreassenAnders M DaleMark LogueKatrina L GrasbyNeda JahanshadJodie N PainterLucia Colodro-CondeJanita BraltenDerrek P HibarPenelope A LindFabrizio PizzagalliJason L SteinPaul M ThompsonSarah E Medlandnull nullPerminder Singh SachdevWilliam S KremenJoanna Marguerite WardlawArno VillringerCornelia M Van DuijnHans Jörgen GrabeWilliam T LongstrethMyriam FornageTomas PausStephanie DebetteMohammad Arfan IkramHelena SchmidtReinhold SchmidtSudha SeshadriPublished in: Nature communications (2020)
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Keyphrases
- genome wide
- dna methylation
- copy number
- cell proliferation
- mental health
- gene expression
- functional connectivity
- resting state
- heart failure
- body composition
- stem cells
- atrial fibrillation
- epithelial mesenchymal transition
- high throughput
- risk factors
- electronic health record
- big data
- multiple sclerosis
- transforming growth factor
- artificial intelligence
- signaling pathway