The genetic landscape of basal ganglia and implications for common brain disorders.

Autor: Bahrami S; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. shahram.bahrami@medisin.uio.no.; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway. shahram.bahrami@medisin.uio.no., Nordengen K; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Neurology, Oslo University Hospital, Oslo, Norway., Rokicki J; Centre of Research and Education in Forensic Psychiatry, Oslo University Hospital, Oslo, Norway., Shadrin AA; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway., Rahman Z; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway., Smeland OB; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Jaholkowski PP; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Parker N; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Parekh P; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., O'Connell KS; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Elvsåshagen T; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Neurology, Oslo University Hospital, Oslo, Norway.; Department of Behavioral Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Toft M; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Neurology, Oslo University Hospital, Oslo, Norway., Djurovic S; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway., Dale AM; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA.; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.; Department of Radiology, University of California, San Diego, La Jolla, CA, USA., Westlye LT; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Psychology, Faculty of Social Sciences, University of Oslo, Oslo, Norway., Kaufmann T; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health, University of Tübingen, Tübingen, Germany.; German Center for Mental Health (DZPG), Tübingen, Germany., Andreassen OA; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. ole.andreassen@medisin.uio.no.; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway. ole.andreassen@medisin.uio.no.; Department of Psychiatry, Oslo University Hospital, Oslo, Norway. ole.andreassen@medisin.uio.no.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 01; Vol. 15 (1), pp. 8476. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1038/s41467-024-52583-0
Abstrakt: The basal ganglia are subcortical brain structures involved in motor control, cognition, and emotion regulation. We conducted univariate and multivariate genome-wide association analyses (GWAS) to explore the genetic architecture of basal ganglia volumes using brain scans obtained from 34,794 Europeans with replication in 4,808 white and generalization in 5,220 non-white Europeans. Our multivariate GWAS identified 72 genetic loci associated with basal ganglia volumes with a replication rate of 55.6% at P < 0.05 and 87.5% showed the same direction, revealing a distributed genetic architecture across basal ganglia structures. Of these, 50 loci were novel, including exonic regions of APOE, NBR1 and HLAA. We examined the genetic overlap between basal ganglia volumes and several neurological and psychiatric disorders. The strongest genetic overlap was between basal ganglia and Parkinson's disease, as supported by robust LD-score regression-based genetic correlations. Mendelian randomization indicated genetic liability to larger striatal volume as potentially causal for Parkinson's disease, in addition to a suggestive causal effect of greater genetic liability to Alzheimer's disease on smaller accumbens. Functional analyses implicated neurogenesis, neuron differentiation and development in basal ganglia volumes. These results enhance our understanding of the genetic architecture and molecular associations of basal ganglia structure and their role in brain disorders.
(© 2024. The Author(s).)
Databáze: MEDLINE
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