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Genetic architecture of subcortical brain structures in 38,851 individuals
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2019 (Engelska)Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 11, s. 1624-+Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

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Nature Publishing Group, 2019. Vol. 51, nr 11, s. 1624-+
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
URN: urn:nbn:se:umu:diva-166483DOI: 10.1038/s41588-019-0511-yISI: 000494714300011PubMedID: 31636452OAI: oai:DiVA.org:umu-166483DiVA, id: diva2:1382093
Forskningsfinansiär
NIH (National Institute of Health), UL1 TR000153NIH (National Institute of Health), R03 AG054936NIH (National Institute of Health), NIH 1 U24 RR021992NIH (National Institute of Health), NIH 1 U24 RR025736-01NIH (National Institute of Health), C06RR029965NIH (National Institute of Health), K99MH102357NIH (National Institute of Health), 5R01MH094524NIH (National Institute of Health), P20GM103472NIH (National Institute of Health), R01MH117601NIH (National Institute of Health), R01MH111671NIH (National Institute of Health), K99MH116115NIH (National Institute of Health), AG047866NIH (National Institute of Health), R01AG059874NIH (National Institute of Health), AG058854NIH (National Institute of Health), R56 AG058854NIH (National Institute of Health), RF1 AG041915NIH (National Institute of Health), U01 AG024904NIH (National Institute of Health), P01 AG026572NIH (National Institute of Health), P30 AG010133NIH (National Institute of Health), R01 AG019771NIH (National Institute of Health), K01 AG049050NIH (National Institute of Health), R01 AG061788NIH (National Institute of Health), P30 AG10133NIH (National Institute of Health), R01AG033193NIH (National Institute of Health), R01AG050631NIH (National Institute of Health), U01AG046161NIH (National Institute of Health), R01AG053960Tillgänglig från: 2020-01-02 Skapad: 2020-01-02 Senast uppdaterad: 2020-01-02Bibliografiskt granskad

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Andersson, MicaelNyberg, Lars

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Satizabal, Claudia L.Adams, Hieab H. H.Knol, Maria J.Teumer, AlexanderChauhan, GaneshAndersson, MicaelStein, Dan J.Walton, EstherStrike, Lachlan T.Westlye, Lars T.Smith, George DaveyNyberg, LarsJönsson, Erik G.Westman, EricFranke, BarbaraChen, Christopher
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Institutionen för integrativ medicinsk biologi (IMB)Umeå centrum för funktionell hjärnavbildning (UFBI)
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Nature Genetics
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