Larger cerebral cortex is genetically correlated with greater frontal area and dorsal thickness
Year: 2023
Type: article
Study design: Observational Study
Abstract: Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e., total surface area, mean cortical thickness) using a genetically informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, where 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recovered loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/frontal-parietal thickness. Interactome-based analyses revealed significant genetic overlap of global and dorsolateral prefrontal modules, enriched for neurodevelopmental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Funders: Government of Canada, Department of Health and Aged Care, Australian Government, Norges Forskningsråd, National Institutes of Health, Canadian Institutes of Health Research, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, Kavli Institute for Brain and Mind, University of California, San Diego, Westlake Education Foundation
Awards: Causes and consequence of human trait variation, G3229869697, G3237229811, Complex trait genomics, Genetic architecture of the human brain and neuropsychiatric disorders, UK Biobank (core renewal), Omic analyses for stratifying Alzheimer's subtypes and identifying novel drug targets, Identifying and quantifying genetic effects on neurodevelopmental trajectories in adolescents, Deciphering the genetic architecture of human complex traits, G8015752676, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, 20/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT VCU, 3/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MINNESOTA, 4/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT FIU, 7/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT YALE, 17/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UCLA, 15/21 ABCD-USA Consortium: Research Project Site at LIBR, 16/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UNIVERSITY OF ROCHESTER, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, ABCD-USA Consortium: Coordinating Center, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, 10/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT SRI, 12/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U PITTSBURGH, 19/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UVM, 1/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U UTAH, 11/21 ABCD-USA Consortium: Research Project Site at UWM, ABCD-USA Consortium: Data Analysis, Informatics and Resource Center, 21/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT WUSTL, 13/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT MUSC, 5/21 ABCD-USA Consortium: Research Project Site at UC San Diego, 18/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT THE UNIVERSITY OF FLORIDA, 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, 14/21 ABCD-USA Consortium: Research Project Site at CU Boulder, G936446435
OpenAlex ID: W4323656752