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Abstract
The molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and multivariate GWAS to two large scale imaging genetic datasets (UK Biobank and the Adolescent Brain Cognitive Development study) to identify and validate genetic association signals. We discover 503 unique genetic loci that have impact on multiple regions of human brain. Among them, more than 79% are validated in either of two large-scale independent imaging datasets. Key molecular pathways involved in axonal growth, astrocyte-mediated neuroinflammation, and synaptogenesis during development are found to significantly impact the measured variations in tissue-specific imaging features. Our results shed new light on the biological determinants of brain tissue composition and their potential overlap with the genetic basis of neuropsychiatric disorders.
12 Authors
Chun Chieh Fan
Robert Loughnan
Carolina Makowski
Diliana Pecheva
Chi-Hua Chen
Donald J. Hagler
Wesley K. Thompson
Nadine Parker
Dennis van der Meer
Oleksandr Frei
Ole A. Andreassen
Anders M. Dale
Enabling scientific discoveries that improve human health