Year: 2023
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Whereas genetic variants influencing total amygdala volume have been identified, the genetic architecture of its distinct nuclei has yet to be explored. We aimed to investigate whether increased phenotypic specificity through nuclei segmentation aids genetic discoverability and elucidates the extent of shared genetic architecture and biological pathways with related disorders. METHODS: T1-weighted brain magnetic resonance imaging scans (N = 36,352, 52% female) from the UK Biobank were segmented into 9 amygdala nuclei with FreeSurfer (version 6.1). Genome-wide association analyses were performed on the entire sample, a European-only subset (n = 31,690), and a generalization (transancestry) subset (n = 4662). We estimated single nucleotide polymorphism-based heritability; derived polygenicity, discoverability, and power estimates; and investigated genetic correlations and shared loci with psychiatric disorders. RESULTS: ) loci in the European analysis, with significant en masse replication for the whole amygdala and central nucleus volumes in the generalization analysis, and we identified 10 additional candidate loci in the combined analysis. The central nucleus had the highest statistical power for discovery. The significantly associated genes and pathways showed unique and shared effects across the nuclei, including immune-related pathways. Shared variants were identified between specific nuclei and autism spectrum disorder, Alzheimer's disease, Parkinson's disease, bipolar disorder, and schizophrenia. CONCLUSIONS: Through investigation of amygdala nuclei volumes, we have identified novel candidate loci in the neurobiology of amygdala volume. These nuclei volumes have unique associations with biological pathways and genetic overlap with psychiatric disorders.
Source: Biological Psychiatry
Institutions: Broad Institute, South African Medical Research Council, University of Cape Town, Stanley Center for Psychiatric Research, Institute of Infectious Disease and Molecular Medicine, Oslo University Hospital, University of Oslo, Maastricht University, University of Tübingen, University of Southern California, University of North Carolina at Chapel Hill, Duke University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Funders: U.S. Department of Veterans Affairs, Sanofi, Office of Research and Development, Sunovion, David and Elaine Potter Foundation, Vistagen Therapeutics, South African Medical Research Council, Fonds National de la Recherche Luxembourg, Universitetet i Oslo, Norges Forskningsråd, Servier, H. Lundbeck A/S, Medical Research Council, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, NIH Clinical Center
OpenAlex ID: W4382358605