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Candidate genes for age at menarche are associated with endometriosis

      Abstract

      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, Pperm ≤ 0.006). Fourteen SNP were associated with the disease within 12 most significant models of gene–gene interactions (Pperm ≤ 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, PFDR = 0.001) and responses to endogenous stimuli (fold enrichment 16.01, PFDR = 0.027).

      Conclusions

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

      Keywords

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      Biography

      Professor Mikhail Churnosov is Head of the Department of Biomedical Disciplines of the Belgorod State University. His areas of research activity include the study of the role of polymorphisms of candidate genes, gene–gene and gene–environmental interactions in the formation of frequently occurring multifactorial diseases among the Russian population.
      Key message
      Sixteen candidate genes for age at menarche were reported to be associated with endometriosis. The observed pleiotropy of these loci suggests a shared genetic architecture for the two phenotypes.