Erratum to: A multi-stage genome-wide association study of uterine fibroids in African Americans.
Erratum to: A multi-stage genome-wide association study of uterine fibroids in African Americans.
复制标题
勘误：非裔美国人子宫肌瘤的多阶段全基因组关联研究。
DOI：
10.1007/s00439-017-1846-z
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发表时间：
2017
期刊：
影响因子：
5.3
通讯作者：
P
中科院分区：
文献类型：
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作者：
Hellwege,JacklynN;Jeff,JaninaM;Wise,LaurenA;Gallagher,CScott;Wellons,Melissa;Hartmann,KatherineE;Jones,SarahF;Torstenson,EricS;Dickinson,Scott;Ruiz-Narváez,EdwardA;Rohland,Nadin;Allen,Alexander;Reich,David;Tandon,Arti;P
子宫肌瘤是子宫的良性肿瘤，影响到77%的绝经期妇女。它们是子宫切除术的主要适应症，在美国每年占340亿美元。种族/民族和年龄是已知的最强风险因素。非裔美国人（AA）女性比欧洲裔美国人女性有更高的患病率，更早的发病，更大和更多的肌瘤。我们进行了一个多阶段的全基因组关联研究（GWAS）的纤维瘤风险的AA妇女，其次是在电脑遗传预测的基因表达谱的顶部命中。在第1阶段，病例和对照通过骨盆成像确认，基因分型并插补到1000个基因组。第2阶段使用来自23andMe，Inc.的自我报告的肌瘤和GWAS数据。和黑人女性健康研究与子宫肌瘤风险的关联使用logistic回归模型进行主成分调整，然后对结果进行荟萃分析。我们观察到3399例AA病例和4764例AA对照在CYTH 4中rs739187（风险等位基因频率= 0.27）存在显著相关性（OR（95%置信区间）= 1.23（1.16-1.30），p值= 7.82 × 10−9）。MetaXcan的遗传相关性评估结果表明，甲状腺组织中CYTH 4的较低预测基因表达与纤维瘤风险显著相关（p值= 5.86 × 10−8）。在这第一个多阶段的GWAS中，我们确定了一个新的风险位点，影响甲状腺基因表达的CYTH 4内的肌瘤，并有潜在的生物学相关性肌瘤。
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 meta-analysis of results. We observed a significant association among 3399 AA cases and 4764 AA controls at rs739187 (risk-allele frequency = 0.27) inCYTH4(OR (95% confidence interval) = 1.23 (1.16–1.30),pvalue = 7.82 × 10−9). Evaluation of the genetic association results with MetaXcan identified lower predicted gene expression ofCYTH4in thyroid tissue as significantly associated with fibroid risk (pvalue = 5.86 × 10−8). In this first multi-stage GWAS for fibroids among AA women, we identified a novel risk locus for fibroids withinCYTH4that impacts gene expression in thyroid and has potential biological relevance for fibroids.