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They are the leading indication for hysterectomy, and account for $34 billion annually in the United States. Race\/ethnicity and age are the strongest known risk factors. African American (AA) women have higher prevalence, earlier onset, and larger and more numerous fibroids than European American women. We conducted a multi-stage genome-wide association study (GWAS) of fibroid risk among AA women followed by\u00a0in silico\u00a0genetically predicted gene expression profiling of top hits. In Stage 1, cases and controls were confirmed by pelvic imaging, genotyped and imputed to 1000 Genomes. Stage 2 used\u00a0self-reported fibroid and GWAS data from 23andMe, Inc. and the Black Women\u2019s Health Study. Associations with fibroid risk were modeled using logistic regression adjusted for principal components, followed by meta-analysis of results. We observed a significant association among 3399 AA cases and 4764 AA controls at rs739187 (risk-allele frequency\u00a0=\u00a00.27) in\u00a0<jats:italic>CYTH4<\/jats:italic> (OR (95% confidence interval)\u00a0=\u00a01.23 (1.16\u20131.30), <jats:italic>p<\/jats:italic> value\u00a0=\u00a07.82\u00a0\u00d7\u00a010<jats:sup>\u22129<\/jats:sup>). Evaluation of the genetic association results with MetaXcan identified lower predicted gene expression of <jats:italic>CYTH4<\/jats:italic>\u00a0in thyroid tissue as significantly associated with fibroid risk (<jats:italic>p<\/jats:italic> value\u00a0=\u00a05.86\u00a0\u00d7\u00a010<jats:sup>\u22128<\/jats:sup>). In this first multi-stage GWAS for fibroids among AA women, we identified a novel risk locus for fibroids within\u00a0<jats:italic>CYTH4<\/jats:italic>\u00a0that impacts gene expression in thyroid and has potential biological relevance for fibroids.<\/jats:p>","DOI":"10.1007\/s00439-017-1836-1","type":"journal-article","created":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T12:00:50Z","timestamp":1503489650000},"page":"1363-1373","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["A multi-stage genome-wide association study of uterine fibroids in African Americans"],"prefix":"10.1007","volume":"136","author":[{"given":"Jacklyn N.","family":"Hellwege","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina M.","family":"Jeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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Hellwege, was originally published Online First without open access. After publication in volume 136, issue 10, page 1363\u20131373 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to \u00a9 The Author(s) 2017 and the article is forthwith distributed under the terms of the Creative Commons Attribution\u00a04.0 International License (\n                    http:\/\/creativecommons.org\/licenses\/by\/4.0\/\n                    \n                ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"DAH is an employee of and owns stock options in 23andMe, Inc. EAS declares the following financial competing interests: consultancy related to uterine fibroids: AbbVie, Allergan, Astellas, Bayer, and Gynesonics, Viteava. Patent applications (pending or actual), including individual applications or those belonging to the institution to which the authors, are affiliated and from which the authors may benefit. US 6440445 (With Nowak, RA, issued 2002, no commercial activity). Research Grants: NIH. R01HD060503, PI. P50 HS023418, Site PI for 3 component parts. R01HD074711, Consultant. K12HD065987, Board Member for Mayo Clinic Site. Other: Focused Ultrasound Surgery Foundation Borah(PI) 11\/15\/11-11\/14\/12 Costs of Uterine Fibroid Treatments Including Focused Ultrasound Surgery. Insightec Inc, PI Patient care costs in conjunction with R01HD60530. In addition, the following non-financial competing interests: relationship (paid or unpaid) with organizations and funding bodies including nongovernmental organizations, research institutions, or charities. Registry Steering Committee, REgistry for Leiomyoma International Efficacy of Focused Ultrasound (RELIEF). Writing or consulting for an educational company. Honoraria from: UpToDate, Massachusetts Medical Society.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}