Russell Mitesh Cerejo, MD

Traylor M, Bevan S, Baron JC, Hassan A, Lewis CM, and Markus HS. Genetic Architecture of Lacunar Stroke. Stroke. 2015 
 
From Dechambre to CM Fisher, we have come along way in understanding the pathogenesis of lacunar strokes. While vascular risk factors play a major role, little is known about its genetics. Dr. Traylor and colleagues in their paper “The genetic architecture of lacunar stroke” set out to investigate the genetics and heritability of lacunar strokes and its subtypes.

They investigated 1029 subjects with MRI confirmed lacunar strokes and 964 controls. The dataset was genotyped on the Illumina HumanExomeCore array, which contains both exome content (~250,000 SNPs) and common tag SNPs (~250,000 SNPs) found on conventional GWAS arrays, and imputed to 1000 Genomes phase 1. The lacunar strokes were sub-typed as follows: isolated lacunar infarcts (ILI) and multiple infarcts and leukoaraiosis (MLI/LA). They used genetic restricted maximum likelihood (GREML) methods to estimate the proportion of phenotypic variance on the liability scale explained by the genetic relationships between individuals based on common SNPs. They also investigated whether the heritability of lacunar stroke was enriched for regulatory sites in the autosome.

They found that lacunar stroke and its subtypes were significantly heritable with estimates being higher for the MLI/LA subtype and slightly lower for the ILI subtype. This heritable component was significantly enriched for sites affecting expression of genes. The two subtypes of lacunar stroke in isolation, but not in combination, was associated with rare variation in the genome, suggesting that they may have distinct genetic susceptibility factors. Such studies are the stepping-stone to understanding the genetic composition of complex diseases and pave way for future studies.