Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.

BACKGROUND

Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.

RESULTS

We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10) (top SNP, rs7921574; β =0.06, P=1.54×10). This locus mapped to an intron of . A trans-ancestry GWAS meta-analysis identified two more loci at (rs10748839; P=2.54×10) and at (rs10786721; P=4.97×10), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression of (rs7897654, β=0.12, P=6.17×10) and (rs10786719, β =-0.17, P=6.60×10) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron of were identified (top SNP, rs35994878; β =0.11, P=2.94×10). For the anterior brain arterial diameter, one locus at was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10).

CONCLUSION

Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.