A multi-stage genome-wide association study of uterine fibroids in African Americans

作者：Hellwege Jacklyn N; Jeff Janina M; Wise Lauren A; Gallagher C Scott; Wellons Melissa; Hartmann Katherine E; Jones Sarah F; Torstenson Eric S; Dickinson Scott; Ruiz Narvaez Edward A; Rohland Nadin; Allen Alexander; Reich David; Tandon Arti; Pasaniuc Bogdan; Mancuso Nicholas; Im Hae Kyung; Hinds David A; Palmer Julie R; Rosenberg Lynn; Denny Joshua C; Roden Dan M; Stewart Elizabeth A; Morton Cynthia C; Kenny Eimear E; Edwards Todd L

来源：Human Genetics, 2017, 136(10): 1363-1373.

DOI：10.1007/s00439-017-1836-1

Uterine fibroids are benign tumors of the uterus affecting up to 77% of women by menopause. 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 in silico genetically 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 self-reported fibroid and GWAS data from 23andMe, Inc. and the Black Women's Health Study. Associations with fibroid risk were modeled using logistic regression adjusted for principal components, followed by metaanalysis of results. We observed a significant association among 3399 AA cases and 4764 AA controls at rs739187 (risk-allele frequency = 0.27) in CYTH4 (OR (95% confidence interval) = 1.23 (1.16-1.30), p value = 7.82 x 10(-9)). Evaluation of the genetic association results with MetaX-can identified lower predicted gene expression of CYTH4 in thyroid tissue as significantly associated with fibroid risk (p value = 5.86 x 10-8). In this first multi-stage GWAS for fibroids among AA women, we identified a novel risk locus for fibroids within CYTH4 that impacts gene expression in thyroid and has potential biological relevance for fibroids.

• 出版日期2017-10
• 单位河北医科大学; MIT