NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke
Document Type
Article
Department
Neurology
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 attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations.
Publication (Name of Journal)
Nature Communications
DOI
10.1038/s41467-024-51819-3
Recommended Citation
Rodriguez-Flores, J. L.,
Khalid, S.,
Parikshak, N.,
Rasheed, A.,
Ye, B.,
Kapoor, M.,
Backman, J.,
Sepehrband, F.,
Gioia, S. D.,
Kamal, A.
(2024). NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke. Nature Communications, 15(1).
Available at:
https://ecommons.aku.edu/pakistan_fhs_mc_med_neurol/269
Comments
Pagination are not provided by the author/publisher.