{"doi":"10.17615/yfz3-kx61","title":"An African-specific haplotype in MRGPRX4 is associated with menthol cigarette smoking","abstract":"In the U.S., more than 80% of African-American smokers use mentholated cigarettes, compared to less than 30% of Caucasian smokers. The reasons for these differences are not well understood. To determine if genetic variation contributes to mentholated cigarette smoking, we performed an exome-wide association analysis in a multiethnic population-based sample from Dallas, TX (N = 561). Findings were replicated in an independent cohort of African Americans from Washington, DC (N = 741). We identified a haplotype of MRGPRX4 (composed of rs7102322[G], encoding N245S, and rs61733596[G], T43T), that was associated with a 5-to-8 fold increase in the odds of menthol cigarette smoking. The variants are present solely in persons of African ancestry. Functional studies indicated that the variant G protein-coupled receptor encoded by MRGPRX4 displays reduced agonism in both arrestin-based and G protein-based assays, and alteration of agonism by menthol. These data indicate that genetic variation in MRGPRX4 contributes to inter-individual and inter-ethnic differences in the preference for mentholated cigarettes, and that the existence of genetic factors predisposing vulnerable populations to mentholated cigarette smoking can inform tobacco control and public health policies.","journal":"UNC Libraries","year":2020,"id":117212,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"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":547389,"name":"L. Pagani","orcid":null,"position":1,"is_corresponding":false},{"id":547390,"name":"D. Risso","orcid":null,"position":2,"is_corresponding":false},{"id":547391,"name":"J. Kozlitina","orcid":null,"position":3,"is_corresponding":false},{"id":547392,"name":"C. Frigerio-Domingues","orcid":null,"position":4,"is_corresponding":false},{"id":547393,"name":"D. Luiselli","orcid":null,"position":5,"is_corresponding":false},{"id":423187,"name":"K. Lansu","orcid":null,"position":6,"is_corresponding":false},{"id":396563,"name":"R.H.J. Olsen","orcid":null,"position":7,"is_corresponding":false},{"id":547394,"name":"B. Roth","orcid":null,"position":8,"is_corresponding":false},{"id":547395,"name":"Anamitra Barik","orcid":null,"position":9,"is_corresponding":false},{"id":547396,"name":"S. Wooding","orcid":null,"position":10,"is_corresponding":false},{"id":547397,"name":"R. Niaura","orcid":null,"position":11,"is_corresponding":false},{"id":547398,"name":"D. Drayna","orcid":null,"position":12,"is_corresponding":false},{"id":547399,"name":"T. Kirchner","orcid":null,"position":13,"is_corresponding":false},{"id":547388,"name":"E. Sainz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:51.309289Z","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":[]}