{"doi":"10.5551/jat.64222","title":"Alcohol Consumption and Cerebral Small- and Large-Vessel Diseases: A Mendelian Randomization Analysis","abstract":"AIMS: It remains inconclusive regarding alcohol intake and stroke risk because determining risk factors depends on the specific pathogenesis of stroke. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in cerebral small- and large-vessel diseases. METHODS: We studied 682 men (mean age, 70.0 years), without stroke, in a cross-sectional Mendelian randomization analysis. We assessed small-vessel diseases (SVDs), which comprised lacunar infarcts, white matter hyperintensities (WMHs), and cerebral microbleeds, and large intracranial artery stenosis (ICAS) on brain magnetic resonance imaging. RESULTS: The median (25%tiles, 75%tiles) alcohol consumption by ALDH2-rs671 inactive A allele (n=313 [45.9%]) and non-A allele (n=369 [54.1%]) carriers was 3.5 (0.0, 16.0) and 32.0 (12.9, 50.0) g/day, respectively. Non-A allele carriers had higher prevalent hypertension and lower low-density lipoprotein cholesterol concentrations than A allele carriers. In age-adjusted ordinal logistic regression for graded burden, odds ratios (95% confidence intervals) for total SVDs, lacunar infarcts, WMHs, cerebral microbleeds, and ICAS in non-Aallele carriers were 1.46 (1.09-1.94), 1.41 (0.95-2.08), 1.39 (1.05-1.85), 1.69 (1.06-2.69), and 0.70 (0.50-0.98), respectively, compared with A allele carriers. These associations attenuated to statistical non-significance after considering covariates and amount of alcohol intake. CONCLUSIONS: Our findings suggest a positive association of alcohol consumption with risk of cerebral SVDs and its inverse association with risk of large-vessel disease through intermediaries, such as hypertension or low-density lipoprotein cholesterol. These findings provide insight into potential causal mechanisms linking alcohol consumption with stroke risk.","journal":"Journal of Atherosclerosis and Thrombosis","year":2023,"id":359713,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9304,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":245390,"name":"Yasuharu Tabara","orcid":"0000-0003-4505-7951","position":1,"is_corresponding":false},{"id":318508,"name":"Aya Kadota","orcid":"0000-0001-7378-0544","position":2,"is_corresponding":false},{"id":930919,"name":"Sayuki Torii","orcid":"0000-0002-3104-9208","position":3,"is_corresponding":false},{"id":373796,"name":"Keiko Kondo","orcid":"0000-0002-9709-4474","position":4,"is_corresponding":false},{"id":22904,"name":"Yuichiro Yano","orcid":"0000-0002-2565-7290","position":5,"is_corresponding":false},{"id":1110672,"name":"Akihiko Shiino","orcid":"0000-0001-6203-9339","position":6,"is_corresponding":false},{"id":1078964,"name":"Kazuhiko Nozaki","orcid":"0000-0003-1623-068X","position":7,"is_corresponding":false},{"id":37773,"name":"Tomonori Okamura","orcid":"0000-0003-0488-0351","position":8,"is_corresponding":false},{"id":37772,"name":"Hirotsugu Ueshima","orcid":"0000-0002-7742-4253","position":9,"is_corresponding":false},{"id":37771,"name":"Katsuyuki Miura","orcid":"0000-0002-2646-9582","position":10,"is_corresponding":false},{"id":373795,"name":"Takashi Hisamatsu","orcid":"0000-0002-6244-1763","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:13:57.361401Z","pmid":"37612092","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}