Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume.
Dina VojinovicHieab H H AdamsXueqiu JianQiong YangAlbert Vernon SmithJoshua C BisAlexander TeumerMarkus ScholzNicola J ArmstrongEdith HoferYasaman SabaMichelle LucianoManon BernardStella TrompetJingyun YangNathan A GillespieSven J Van der LeeAlexander NeumannShahzad AhmadOle Andreas AndreassenDavid AmesNajaf AminKonstantinos ArfanakisMark E BastinDiane M BeckerAlexa S BeiserFrauke BeyerHenry BrodatyR Nick BryanRobin BülowAnders M DalePhilip Lawrence De JagerIan J DearyCharles DeCarliDebra A FleischmanRebecca F GottesmanJeroen van der GrondVilmundur G GudnasonTamara B HarrisGeorg HomuthDavid S KnopmanJohn B KwokCora E LewisShuo LiMarkus LoefflerOscar L LopezPauline MaillardHanan El MarrounKaren A MatherThomas H MosleyRyan L MuetzelMatthias NauckPaul A NyquistMatthew S PanizzonZdenka PausovaBruce M PsatyKen RiceJerome I RotterNatalie RoyleClaudia L SatizabalReinhold SchmidtPeter R SchofieldPamela J SchreinerStephen SidneyDavid J StottAnbupalam ThalamuthuAndre G UitterlindenMaria C Valdés HernándezMeike W VernooijWei WenTonya WhiteA Veronica WitteKatharina WittfeldMargaret J WrightLisa R YanekHenning TiemeierWilliam S KremenDavid A BennettJ Wouter JukemaTomas PausJoanna Marguerite WardlawHelena SchmidtPerminder Singh SachdevArno VillringerHans Jörgen GrabeW T LongstrethCornelia M van DuijnLenore J LaunerSudha SeshadriMohammad Arfan IkramMyriam FornagePublished in: Nature communications (2018)
The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.