{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:37:26Z","timestamp":1792816646161,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n To identify heritable factors that affect BMI among Indigenous Americans, we previously conducted a genome\u2010wide association study using 7.9 million imputed genetic variants from 6789 participants. This study sought to identify a mechanistic link between variants with the strongest association with BMI and adipocyte metabolism.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Variants with the strongest association with BMI (rs114857151, rs187498396, and rs189879565;\n r<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090.99, 2.7% increase in BMI per risk allele,\n p<\/jats:italic>\n \u2009=\u20094\u2009\u00d7\u200910\n \u22127<\/jats:sup>\n , adjusted for age, sex, birth year, and the first five genetic principal components) were functionally analyzed using luciferase assays.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n These variants map to\n CYP26B1<\/jats:italic>\n , which encodes an enzyme involved in retinoic acid (RA) metabolism. In\u00a0vitro studies showed that the haplotype with the three risk (higher BMI) variants had a 23% decrease in\n CYP26B1<\/jats:italic>\n transcript variant 3 (TV3) promoter activity. RA response element reporter assays showed that the Cyp26b1 TV3 isoform might be important for RA homeostasis in adipocytes.\n Cyp26b1<\/jats:italic>\n TV3 knockdown in mouse OP9 adipocytes resulted in increased Aldh1a1 expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Alleles carrying these three variants may have reduced expression of\n CYP26B1<\/jats:italic>\n TV3 which in turn influences RA signaling and adipocyte metabolism, providing a possible mechanistic link between\n CYP26B1<\/jats:italic>\n variation and BMI.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/oby.70320","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:54:20Z","timestamp":1792814060000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Characterization of\n \n CYP26B1<\/i>\n <\/scp>\n Short Isoform as a Novel Locus for Obesity in Indigenous Americans From Arizona"],"prefix":"10.1002","author":[{"given":"Fehmida Farid","family":"Khan","sequence":"first","affiliation":[{"name":"Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Traurig","sequence":"additional","affiliation":[{"name":"Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendrick","family":"Freeland","sequence":"additional","affiliation":[{"name":"Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4252-7068","authenticated-orcid":false,"given":"Robert L.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-9161","authenticated-orcid":false,"given":"Paolo","family":"Piaggi","sequence":"additional","affiliation":[{"name":"Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-9670","authenticated-orcid":false,"given":"Leslie J.","family":"Baier","sequence":"additional","affiliation":[{"name":"Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Obesity: Preventing and Managing the Global Epidemic. 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