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  Genetic architecture of the white matter connectome of the human brain

Sha, Z., Schijven, D., Fisher, S. E., & Francks, C. (2022). Genetic architecture of the white matter connectome of the human brain. bioRxiv, 2022.05.10.491289. doi:10.1101/2022.05.10.491289.

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Sha, Zhiqiang1, Author              
Schijven, Dick1, Author              
Fisher, Simon E.1, Author              
Francks, Clyde1, 2, Author              
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1Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
2Imaging Genomics, MPI for Psycholinguistics, Max Planck Society, ou_2579692              

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 Abstract: White matter tracts form the structural basis of large-scale functional networks in the human brain. We applied brain-wide tractography to diffusion images from 30,810 adult participants (UK Biobank), and found significant heritability for 90 regional connectivity measures and 851 tract-wise connectivity measures. Multivariate genome- wide association analyses identified 355 independently associated lead SNPs across the genome, of which 77% had not been previously associated with human brain metrics. Enrichment analyses implicated neurodevelopmental processes including neurogenesis, neural differentiation, neural migration, neural projection guidance, and axon development, as well as prenatal brain expression especially in stem cells, astrocytes, microglia and neurons. We used the multivariate association profiles of lead SNPs to identify 26 genomic loci implicated in structural connectivity between core regions of the left-hemisphere language network, and also identified 6 loci associated with hemispheric left-right asymmetry of structural connectivity. Polygenic scores for schizophrenia, bipolar disorder, autism spectrum disorder, attention-deficit hyperactivity disorder, left-handedness, Alzheimer’s disease, amyotrophic lateral sclerosis, and epilepsy showed significant multivariate associations with structural connectivity, each implicating distinct sets of brain regions with trait-relevant functional profiles. This large-scale mapping study revealed common genetic contributions to the structural connectome of the human brain in the general adult population, highlighting links with polygenic disposition to brain disorders and behavioural traits.

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Language(s): eng - English
 Dates: 2022-05-11
 Publication Status: Published online
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 Rev. Type: No review
 Identifiers: DOI: 10.1101/2022.05.10.491289
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Title: bioRxiv
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Pages: - Volume / Issue: - Sequence Number: 2022.05.10.491289 Start / End Page: - Identifier: -