NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke.

ABSTRACT: The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10^-9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10^-10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10^-6). The variant is att

SUBMITTER: Rodriguez-Flores JL 

PROVIDER: S-EPMC11399414 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature