Association of Chr17q25 with cerebral white matter hyperintensities and cognitive impairment: the J- SHIPP study.

Background and purpose A recent genome-wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non- European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function. Methods Study subjects were 1190 general Japanese persons (66.0 ± 8.9 years old). Asymptomatic cerebrovascular damage, including lacunar infarctions, microbleeds, periventricular hyperintensity and deep and subcortical white matter hyperintensity ( DSWMH), was evaluated by brain magnetic resonance imaging. Results A polymorphism rs3744028 was significantly associated with DSWMH grade ( P = 0.015) but not periventricular hyperintensity, lacunar infarction, and microbleeds. Although age, hypertension, insulin resistance, B-type natriuretic peptide, and carotid atherosclerosis were also correlated with DSWMH, association of the genotype was independent of these environmental risk factors. In contrast, the risk allele had a protective effect against reduced cognitive function. Conclusion Susceptibility of the 17q25 locus may be conserved beyond ethnic differences. Genetic variants may have bipolar effects on brain histological and functional changes. [ABSTRACT FROM AUTHOR]