Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants

Cerebral small vessel disease is a major cause of stroke and dementia, but its genetic basis is incompletely understood. We perform a genetic study of three MRI markers of the disease in UK Biobank imaging data and other sources: white matter hyperintensities (N=42,310), fractional anisotropy (N=17,663) and mean diffusivity (N=17,467). Our aim is to better understand the disease pathophysiology. Across the three traits, we identify 31 loci, of which 21 were previously unreported. We perform a transcriptome-wide association study to identify associations with gene expression in relevant tissues, identifying 66 associated genes across the three traits. This genetic study provides insights into the understanding of the biological mechanisms underlying small vessel disease. Cerebral small vessel disease (CSVD) is a major cause of stroke and associated with structural changes of the brain. Here, Persyn et al. perform genome-wide association studies for magnetic resonance imaging (MRI) markers of CSVD, explore genetic correlations and prioritize candidate genes.