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Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain.

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.

SUBMITTER: Fan CC

PROVIDER: S-EPMC9065144 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain.

Fan Chun Chieh CC Loughnan Robert R Makowski Carolina C Pecheva Diliana D Chen Chi-Hua CH Hagler Donald J DJ Thompson Wesley K WK Parker Nadine N van der Meer Dennis D Frei Oleksandr O Andreassen Ole A OA Dale Anders M AM

Nature communications 20220503 1

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 uni ...[more]

PMID: 35505052

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Dataset Information

Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain.

Publications

Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain.

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