Research question

Are the candidate genes for age at menarche associated with a risk of endometriosis?

Design

Fifty-two candidate single nucleotide polymorphisms (SNP) for age at menarche, their gene–gene and gene–environment interactions were analysed for possible association with endometriosis in a sample of 395 patients and 981 controls. Association of the polymorphisms was analysed using logistic regression according to three main genetic models (additive, recessive and dominant). The gene–gene and gene–environment interactions were analysed for the second-, third- and fourth-order models with adjustment for covariates and multiple comparisons with subsequent cross-validation.

Results

Sixteen SNP for age at menarche out of the 52 studied were associated with endometriosis. Polymorphism rs6589964 BSX was associated with endometriosis according to the additive and recessive models (OR 1.27–1.47, P_perm ≤ 0.006). Fourteen SNP were associated with the disease within 12 most significant models of gene–gene interactions (P_perm ≤ 0.008). Twelve SNP involved in 10 most significant models of SNP–induced abortion interactions are associated with endometriosis. Fourteen of the 16 polymorphisms associated with endometriosis demonstrated pleiotropic effects: they were also associated with either age at menarche (7 SNP) or height and/or body mass index (10 SNP) in the studied sample. The 16 SNP associated with endometriosis and 316 SNP linked to them have regulatory and expression quantitative trait locus significance for 28 genes contributing to the G alpha signal pathway (fold enrichment 31.09, P_FDR = 0.001) and responses to endogenous stimuli (fold enrichment 16.01, P_FDR = 0.027).

Conclusions

Sixteen SNP for age at menarche out of the 52 studied were associated with endometriosis.

中文翻译：

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月经初潮年龄的候选基因与子宫内膜异位症有关

研究问题

月经初潮年龄的候选基因是否与子宫内膜异位症的风险有关？

设计

在 395 名患者和 981 名对照样本中，分析了 52 个与月经初潮年龄相关的候选单核苷酸多态性 (SNP)，分析了它们的基因-基因和基因-环境相互作用可能与子宫内膜异位症的关联。根据三个主要遗传模型（加性、隐性和显性）使用逻辑回归分析多态性的关联。分析了二阶、三阶和四阶模型的基因 - 基因和基因 - 环境相互作用，并调整了协变量和多重比较以及随后的交叉验证。

结果

在所研究的 52 个初潮年龄 SNP 中有 16 个与子宫内膜异位症有关。根据加性和隐性模型（OR 1.27–1.47，P _perm  ≤ 0.006），多态性 rs6589964 BSX与子宫内膜异位症相关。在 12 个最重要的基因-基因相互作用模型中，14 个 SNP 与疾病相关（P _perm ≤ 0.008)。涉及 10 个最重要的 SNP 诱导流产相互作用模型的 12 个 SNP 与子宫内膜异位症有关。与子宫内膜异位症相关的 16 种多态性中有 14 种表现出多效性：它们还与研究样本中的初潮年龄 (7 SNP) 或身高和/或体重指数 (10 SNP) 相关。与子宫内膜异位症相关的 16 个 SNP 和与其相关的 316 个 SNP 对参与 G α 信号通路的 28 个基因（富集倍数 31.09，P _FDR  = 0.001）和对内源性刺激的反应（富集倍数 16.01，P _FDR  = 0.027)。

结论

在所研究的 52 个初潮年龄 SNP 中有 16 个与子宫内膜异位症有关。