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Common genetic variants influence human subcortical brain structures
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2015 (Engelska)Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 520, nr 7546, s. 224-U216Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume(5) and intracranial volume(6). These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 X 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Ort, förlag, år, upplaga, sidor
2015. Vol. 520, nr 7546, s. 224-U216
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-102344DOI: 10.1038/nature14101ISI: 000352454600040PubMedID: 25607358Scopus ID: 2-s2.0-84926395609OAI: oai:DiVA.org:umu-102344DiVA, id: diva2:825380
Forskningsfinansiär
Swedish National Infrastructure for Computing (SNIC), SNIC2014-1-4Tillgänglig från: 2015-06-23 Skapad: 2015-04-23 Senast uppdaterad: 2023-03-24Bibliografiskt granskad

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Andersson, MicaelSalami, AlirezaNyberg, Lars

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Andersson, MicaelSalami, AlirezaNyberg, Lars
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