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Genome-wide association analysis of young onset stroke identifies a locus on chromosome 10q25 near HABP2.
Stroke 47, 307-316 (2016)
Verlagsversion Forschungsdaten DOI
BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years. METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Factor Vii ; Genetics ; Genome-wide Analysis ; Ischemic Stroke ; Stroke; Vii-activating Protease; Antihypertensive Drug Therapies; Acute Ischemic-stroke; Factor-v-leiden; Causative Classification; Atherosclerotic Stroke; Atrial-fibrillation; Follow-up; Risk; Genetics
ISSN (print) / ISBN 0039-2499
Quellenangaben Band: 47, Heft: 2, Seiten: 307-316
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed