Multi-population Genome-Wide Association Study Identifies Multiple Novel Loci associated with Asymptomatic Intracranial Large Artery Stenosis
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Background
Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.
Methods and Results
This study included 4960 participants from seven geographically diverse population-based cohorts (34% Whites, 16% African Americans, 22% Hispanics, 24% Asians, 5% native Ecuadorians). We defined asymptomatic ILAS as luminal stenosis > 50% in any large brain artery using time-of-flight magnetic resonance angiography (MRA). A genome-wide association study revealed one variant in RP11-552D8.1 (rs75615271; OR, 1.22 [1.11-1.33]; P =4.85×10 −8 ) associated with global ILAS at genome-wide significance ( P <5×10 −8 ). Gene-based association analysis identified a gene-set enriched in chr1q32 region, including NEK2 , LPGAT1 , INTS7 , DTL , and TMEM206 , in global ILAS ( P =1.34 ×10 −7 ) and anterior ILAS ( P =1.77 ×10 −8 ).
Conclusion
This study reveals one variant rs75615271 associated with asymptomatic ILAS in a multi-population. Further functional studies may help elucidate the role that this variant plays in the pathophysiology of asymptomatic ILAS.
