Abstract
Introduction:
Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets generalizable also to later-onset disease. Few studies have investigated the sex-specific genetic associations with early-onset ischemic stroke even though several features of ischemic stroke differ between males and females. We hypothesized that stratifying the GWAS by sex would reveal novel stroke loci.
Methods:
We performed a transethnic ischemic stroke GWAS of 3,056 female cases and 4,462 male cases < 60 years-old and 16,192 and 16,048 sex-matched controls, respectively, from the Early Onset Stroke Genetics Consortium.
Results:
We identified a significant association in women with a locus in close proximity to
TMX1
, a transmembrane platelet protein that inhibits platelet function. Additionally, we identified 2 other suggestive (P < 5 x 10
-6
) loci in females (see Table), i.e., at
APOH
, which encodes beta2-glycoprotein I, an established GWAS locus for lipoprotein(a), and
LRFN2
which has been previously reported to associate with obesity-related measures and type II diabetes. We observed suggestive evidence for association in males with
MMP3/MMP12
, a known stroke susceptibility locus.
Conclusions:
Despite a very modest sample size, sex-specific analyses identified suggestive associations at biologically important novel loci in females and a known stroke locus in males. Further studies of sex-specific associations in both early- and later-onset ischemic stroke are needed.
