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首页> 外文期刊>PLoS Genetics >African genetic ancestry interacts with body mass index to modify risk for uterine fibroids
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African genetic ancestry interacts with body mass index to modify risk for uterine fibroids

机译：非洲遗传祖先与体重指数相互作用，以修改子宫肌瘤的风险

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Race, specifically African ancestry, and obesity are important risk factors for uterine fibroids, and likely interact to provide the right conditions for fibroid growth. However, existing studies largely focus on the main-effects rather than their interaction. Here, we firstly provide evidence for interaction between categories of body mass index (BMI) and reported-race in relation to uterine fibroids. We then investigate whether the association between inferred local European ancestry and fibroid risk is modified by BMI in African American (AA) women in the Vanderbilt University Medical Center bio-repository (BioVU) (539 cases and 794 controls) and the Coronary Artery Risk Development in Young Adults study (CARDIA, 264 cases and 173 controls). We used multiple logistic regression to evaluate interactions between local European ancestry and BMI in relation to fibroid risk, then performed fixed effects meta-analysis. Statistical significance threshold for local-ancestry and BMI interactions was empirically estimated with 10,000 permutations (p-value = 1.18x10-4). Admixture mapping detected an association between European ancestry and fibroid risk which was modified by BMI (continuous-interaction p-value = 3.75x10-5) around ADTRP (chromosome 6p24); the strongest association was found in the obese category (ancestry odds ratio (AOR) = 0.51, p-value = 2.23x10-5). Evaluation of interaction between genotyped/imputed variants and BMI in this targeted region suggested race-specific interaction, present in AAs only; strongest evidence was found for insertion/deletion variant (6:11946435), again in the obese category (OR = 1.66, p-value = 1.72x10-6). We found nominal evidence for interaction between local ancestry and BMI at a previously reported region in chromosome 2q31-32, which includes COL5A2, and TFPI, an immediate downstream target of ADTRP. Interactions between BMI and SNPs (single nucleotide polymorphisms) found in this region in AA women were also detected in an independent European American population of 1,195 cases and 1,164 controls. Findings from our study provide an example of how modifiable and non-modifiable factors may interact to influence fibroid risk and suggest a biological role for BMI in fibroid etiology.
机译：种族，特别是非洲血统，肥胖是子宫肌瘤的重要危险因素，并且可能相互作用，为肌瘤生长提供正确的条件。然而，现有研究主要集中在主要效应上，而不是它们的互动。在这里，我们首先提供了体重指数（BMI）类别之间的相互作用的证据，并与子宫肌瘤有关的报告。然后，我们调查推断本地欧洲祖先和肌瘤风险之间的关联是否由BMI在Vanderbilt University Center生物储存库（Biovu）（Biovu）（539例和794个对照组）和冠状动脉风险发展中的非洲裔美国人（AA）妇女进行修改在年轻的成年人学习（Cardia，264例和173个控制）中。我们使用多元的逻辑回归来评估当地欧洲血统和BMI之间的相互作用与肌瘤风险有关，然后进行了固定效应META分析。局部祖先和BMI相互作用的统计显着性阈值被凭经验估计了10,000个排列（P值= 1.18x10-4）。混合物映射检测到欧洲血统和肌瘤风险之间的关联，其由BMI（连续相互作用p值= 3.75x10-5）周围修饰（染色体6p24）;在肥胖类别中发现了最强的关联（祖先赔率比（AOR）= 0.51，P值= 2.23x10-5）。在该靶向区域中基因分型/抵抗变体与BMI之间的相互作用的评价表明，仅在AAS中存在种族特异性相互作用;发现插入/删除变体（6：11946435），在肥胖类别（或= 1.66，p值= 1.72x10-6）中，发现了最强的证据。我们在先前报告的染色体中的染色体的区域，其中包括COL5A2和TFPI，ADTRP的即时下游靶标在先前报告的地区，在先前报告的地区，发现了名义上的依据进行了局部祖先和BMI之间的相互作用。在AA妇女中发现的BMI和SNPS（单核苷酸多态性）之间的相互作用也被检测到在一个1,195例和1,164个对照的独立欧洲人口中检测到。我们研究的结果提供了可修改和不可修改因素的例子可以相互作用以影响肌瘤风险，并表明BMI在纤维病因中的生物学作用。

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