l e t t e r s Saccular intracranial aneurysms are balloon-like dilations of the intracranial arte... more l e t t e r s Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,89 cases and 4,8 controls with 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 8q.2 (odds ratio (OR) = .22, P = . × 0 −2 ), STARD13-KL on 3q3. (OR = .20, P = 2.5 × 0 −9 ) and a gene-rich region on 0q24.32 (OR = .29, P = .2 × 0 −9 ). We also confirmed prior associations near SOX17 (8q.23-q2.; OR = .28, P = .3 × 0 −2 ) and CDKN2A-CDKN2B (9p2.3; OR = .3, P = .5 × 0 −22 ). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.
l e t t e r s Saccular intracranial aneurysms are balloon-like dilations of the intracranial arte... more l e t t e r s Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,89 cases and 4,8 controls with 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 8q.2 (odds ratio (OR) = .22, P = . × 0 −2 ), STARD13-KL on 3q3. (OR = .20, P = 2.5 × 0 −9 ) and a gene-rich region on 0q24.32 (OR = .29, P = .2 × 0 −9 ). We also confirmed prior associations near SOX17 (8q.23-q2.; OR = .28, P = .3 × 0 −2 ) and CDKN2A-CDKN2B (9p2.3; OR = .3, P = .5 × 0 −22 ). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.
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Papers by Nikhil Mane