{"doi":"10.1101/2025.05.06.25327093","title":"Multi-population Genome-Wide Association Study Identifies Multiple Novel Loci associated with Asymptomatic Intracranial Large Artery Stenosis","abstract":"ABSTRACT Background Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood. Methods and Results This study included 4960 participants from seven geographically diverse population-based cohorts (34% Whites, 16% African Americans, 22% Hispanics, 24% Asians, 5% native Ecuadorians). We defined asymptomatic ILAS as luminal stenosis > 50% in any large brain artery using time-of-flight magnetic resonance angiography (MRA). A genome-wide association study revealed one variant in RP11-552D8.1 (rs75615271; OR, 1.22 [1.11-1.33]; P =4.85×10 −8 ) associated with global ILAS at genome-wide significance ( P <5×10 −8 ). Gene-based association analysis identified a gene-set enriched in chr1q32 region, including NEK2 , LPGAT1 , INTS7 , DTL , and TMEM206 , in global ILAS ( P =1.34 ×10 −7 ) and anterior ILAS ( P =1.77 ×10 −8 ). Conclusion This study reveals one variant rs75615271 associated with asymptomatic ILAS in a multi-population. Further functional studies may help elucidate the role that this variant plays in the pathophysiology of asymptomatic ILAS.","journal":"medRxiv","year":2025,"id":565450,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650105,"name":"Farid Khasiyev","orcid":"0000-0002-3127-0973","position":1,"is_corresponding":false},{"id":741269,"name":"Antonio Spagnolo‐Allende","orcid":"0000-0001-6057-4469","position":2,"is_corresponding":false},{"id":932098,"name":"Danurys Sanchez","orcid":"0000-0001-8273-0952","position":3,"is_corresponding":false},{"id":268366,"name":"Howard Andrews","orcid":"0000-0002-7726-0551","position":4,"is_corresponding":false},{"id":275021,"name":"Qiong Yang","orcid":"0000-0002-3658-1375","position":5,"is_corresponding":false},{"id":245376,"name":"Alexa Beiser","orcid":"0000-0001-8551-7778","position":6,"is_corresponding":false},{"id":447295,"name":"Ye Qiao","orcid":"0000-0002-0499-9283","position":7,"is_corresponding":false},{"id":91710,"name":"José R. 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