{"doi":"10.1002/oby.23359","title":"Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity","abstract":"OBJECTIVE: This study aimed to identify genetic variants enriched in Southwest American Indian (SWAI) individuals that associate with BMI. METHODS: Whole genome sequencing data (n = 296) were used to identify potentially functional variants that are common in SWAI individuals (minor allele frequency ≥10%) but rare in other ethnic groups (minor allele frequency < 0.1%). Enriched variants were tested for association with BMI in 5,870 SWAI individuals. One variant was studied using a luciferase reporter, and haplotypes that included this variant were analyzed for association with various measures of obesity (n = 917-5,870), 24-hour energy expenditure (24-h EE; n = 419), and skeletal muscle biopsy expression data (n = 207). RESULTS: A 5' untranslated region variant in cytochrome b5 type A (CYB5A), rs548402150, met the enrichment criteria and associated with increased BMI (β = 2%, p = 0.004). Functionally, rs548402150 decreased luciferase expression by 30% (p = 0.003) and correlated with decreased skeletal muscle CYB5A expression (β = -0.5 SD, p = 0.0008). Combining rs548402150 with two splicing quantitative trait loci in CYB5A identified a haplotype carried almost exclusively in SWAI individuals that associated with increased BMI (β = 3%, p = 0.0003) and decreased CYB5A expression, whereas the most common haplotype in all ethnic groups associated with lower BMI and percentage of body fatness, increased 24-h EE, and increased CYB5A expression. CONCLUSIONS: Further studies on the effects of CYB5A on 24-h EE and BMI may provide insights into obesity-related physiology.","journal":"Obesity","year":2022,"id":276271,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8931,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":534642,"name":"Michael Traurig","orcid":null,"position":1,"is_corresponding":false},{"id":946414,"name":"Pankaj Kumar","orcid":"0000-0002-5428-5860","position":2,"is_corresponding":false},{"id":260537,"name":"Paolo Piaggi","orcid":"0000-0003-2774-9161","position":3,"is_corresponding":false},{"id":522441,"name":"Çiğdem Köroğlu","orcid":"0000-0002-6778-4773","position":4,"is_corresponding":false},{"id":440862,"name":"Sayuko Kobes","orcid":null,"position":5,"is_corresponding":false},{"id":439831,"name":"Robert L. Hanson","orcid":"0000-0002-4252-7068","position":6,"is_corresponding":false},{"id":522447,"name":"Clifton Bogardus","orcid":"0000-0003-1472-3376","position":7,"is_corresponding":false},{"id":439829,"name":"Leslie J. Baier","orcid":"0000-0002-8773-9670","position":8,"is_corresponding":false},{"id":747467,"name":"Samantha E. Day","orcid":"0000-0002-9818-0972","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:28:26.545826Z","pmid":"35043601","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":[]}