Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study

Area of Science:

• Neuroimaging genetics
• Brain structure and function
• Genetic pleiotropy

Background:

• Genetic pleiotropy is common across brain characteristics from single neuroimaging modalities like MRI.
• Understanding cross-modality pleiotropy is key to integrating brain function, micro-, and macrostructure.

Purpose of the Study:

• To investigate genetic overlap across structural, functional, and diffusion MRI phenotypes.
• To identify shared genetic mechanisms influencing brain morphology, connectivity, and tissue composition.
• To enhance the discovery of genetic loci and genes by jointly analyzing multimodal neuroimaging data.

Main Methods:

• Genome-wide association study (GWAS) using the Multivariate Omnibus Statistical Test (MOSTest) on multimodal neuroimaging data.
• Analysis of large datasets from the UK Biobank (N=34,029) and ABCD Study (N=8607).
• Identification of cross-modality genes and their biological functions, including prenatal brain development expression.

Main Results:

• Extensive genetic overlap was found across neuroimaging modalities at locus and gene levels.
• Joint analysis boosted the discovery of genetic loci and genes beyond individual modality analyses.
• Cross-modality genes are involved in fundamental biological processes and prenatal brain development.

Conclusions:

• Multimodal neuroimaging analysis reveals shared genetic underpinnings of brain structure, function, and tissue composition.
• This approach enhances the identification of genetic factors influencing brain phenotypes.
• Findings improve the prediction of psychiatric disorders by leveraging multimodal genetic insights.