The genetic architecture of human brainstem structures and their involvement in common brain disorders.
Torbjørn ElvsåshagenShahram BahramiDennis van der MeerIngrid AgartzDag AlnaesDeanna M BarchRamona Baur-StreubelAlessandro BertolinoMona K BeyerGiuseppe BlasiStefan BorgwardtBirgitte BoyeJan K BuitelaarErlend BøenElisabeth Gulowsen CeliusSimon CervenkaAnnette ConzelmannDavid CoynelPasquale Di CarloSrdjan DjurovicSarah EisenacherThomas EspesethHelena Fatouros-BergmanLena FlycktBarbara FrankeOleksandr FreiBarbara FrankeHanne Flinstad HarboCatharina A HartmanAsta HåbergDirk HeslenfeldPieter J HoekstraEinar August HøgestølRune JonassenErik G Jönssonnull nullMartina KirschIwona KłoszewskaTrine Vik LagerbergNils Inge LandrøStephanie Le HellardKlaus-Peter LeschLuigi A MaglanocUlrik F MaltPatrizia MecocciIngrid MelleAndreas Meyer-LindenbergTorgeir MobergetJan Egil NordvikLars NybergKevin Sean O'ConnellJaap OosterlaanMarco PapalinoAndreas PapassotiropoulosPaul PauliGiulio PergolaKarin PerssonDominique de QuervainAndreas ReifJaroslav RokickiDaan van RooijAlexey A ShadrinAndré SchmidtEmanuel SchwarzGeir SelbaekHilkka SoininenPiotr SowaVidar M SteenMagdalini TsolakiBruno VellasLei WangErik WestmanGeorg C ZieglerMathias ZinkOle A AndreassenLars Tjelta WestlyeTobias KaufmannPublished in: Nature communications (2020)
Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Keyphrases
- genome wide
- mild cognitive impairment
- bipolar disorder
- white matter
- multiple sclerosis
- resting state
- copy number
- cognitive decline
- dna methylation
- high resolution
- cerebral ischemia
- electronic health record
- major depressive disorder
- functional connectivity
- mental health
- big data
- subarachnoid hemorrhage
- brain injury
- blood brain barrier
- genome wide analysis