{"doi":"10.17615/73za-5242","title":"Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults","abstract":"Plasma homocysteine (Hcy) level is associated with cardiovascular disease and may play an etiologic role in vascular damage, a precursor for atherosclerosis. We performed a genome-wide association study for Hcy in 1786 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The most strongly associated single-nucleotide polymorphism (SNP) (rs7422339, P = 4.7 × 10−13) encodes Thr1405Asn in the gene CPS1 and explained 3.0% of variation in the Hcy level. The widely studied MTHFR C677T SNP (rs1801133) was also highly significant (P = 8.7 × 10−10) and explained 1.6% of the trait variation. We also genotyped these two SNPs in 1679 CLHNS young adult offspring. The MTHFR C677T SNP was strongly associated with Hcy (P = 1.9 × 10−26) and explained ∼5.1% of the variation in the offspring. In contrast, the CPS1 variant was significant only in females (P = 0.11 in all; P = 0.0087 in females). Combined analysis of all samples confirmed that the MTHFR variant was more strongly associated with Hcy in the offspring (interaction P = 1.2 × 10−5). Furthermore, although there was evidence for a positive synergistic effect between the CPS1 and MTHFR SNPs in the offspring (interaction P = 0.0046), there was no significant evidence for an interaction in the mothers (P = 0.55). These data confirm a recent finding that CPS1 is a locus influencing Hcy levels in women and suggest that genetic effects on Hcy may differ across developmental stages.","journal":"UNC Libraries","year":2020,"id":143990,"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":0.9007,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":548235,"name":"Amanda F. Marvelle","orcid":null,"position":1,"is_corresponding":false},{"id":496974,"name":"Thomas W. McDade","orcid":"0000-0001-5829-648X","position":2,"is_corresponding":false},{"id":331568,"name":"Yunfei Wang","orcid":"0000-0002-3899-1095","position":3,"is_corresponding":false},{"id":22011,"name":"Damien C. Croteau‐Chonka","orcid":"0000-0003-3466-1846","position":4,"is_corresponding":false},{"id":324988,"name":"Judith B. Borja","orcid":null,"position":5,"is_corresponding":false},{"id":11271,"name":"Karen L. Mohlke","orcid":"0000-0001-6721-153X","position":6,"is_corresponding":false},{"id":24984,"name":"Leslie A. Lange","orcid":"0000-0002-4220-6766","position":7,"is_corresponding":false},{"id":324211,"name":"Linda S. Adair","orcid":"0000-0002-3670-8073","position":8,"is_corresponding":false},{"id":16068,"name":"Kyle J. Gaulton","orcid":"0000-0003-1318-7161","position":9,"is_corresponding":false},{"id":11309,"name":"Ethan M. Lange","orcid":"0000-0001-7075-4287","position":10,"is_corresponding":false},{"id":24805,"name":"Yun Li","orcid":"0000-0002-9275-4189","position":11,"is_corresponding":false},{"id":533598,"name":"Christopher W. Kuzawa","orcid":"0000-0002-0649-8677","position":12,"is_corresponding":false},{"id":385994,"name":"Qin Li","orcid":"0000-0002-8633-8859","position":13,"is_corresponding":false},{"id":43059,"name":"Shawn Levy","orcid":"0000-0002-1369-5740","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:41.821196Z","pmid":null,"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":[]}