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

Nat Commun. 2020 May 1;11(1):2175. doi: 10.1038/s41467-020-15932-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Cerebral Small Vessel Diseases / complications
  • Cerebral Small Vessel Diseases / diagnostic imaging*
  • Cerebral Small Vessel Diseases / genetics*
  • Female
  • Gene Expression Regulation / genetics
  • Gene Ontology
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / genetics
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Specificity
  • Polymorphism, Single Nucleotide
  • Stroke / genetics*
  • Transcriptome / genetics


  • Biomarkers