Twelve loci provide insights into the genetic basis of lacunar stroke and small vessel disease: a meta-analysis of genome-wide association studies
Abstract
We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar
stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of
the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium.
Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a
transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with
a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic
associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated
with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and
evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation.