Polymorphisms of the <i>TNF</i>, <i>LTA</i>, and <i>TNFRSF1B</i> genes are associated with onsets of menarche and menopause in US women of European ancestry
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The <i>TNF</i>, <i>LTA</i> and <i>TNFRSF1B</i> genes have been implicated in various traits related to menarche and menopause. To analyse the <i>TNF</i>, <i>LTA</i> and <i>TNFRSF1B</i> genes for their association with ages at menarche (AM) and natural menopause (ANM). The study sample consisted of 314 unrelated females of European ancestry. Twenty SNPs located in and near the genes were analysed using various statistical methods. In addition, the functional significance of the loci associated with AM and ANM was analysed <i>in silico</i>. Locus rs2229094 of the <i>LTA</i> gene was associated with AM according to the additive (<i>β</i> = −0.295, <i>p</i><sub>perm</sub> = 0.016) and recessive (<i>β</i> = −0.940, <i>p</i><sub>perm</sub> = 0.016) genetic models. Haplotype GG rs1148459-rs590368 of the <i>TNFRSF1B</i> gene was associated with AM (<i>β</i> = 0.307, <i>p</i><sub>perm</sub> = 0.023). Haplotype GCA rs2844484-rs2229094-rs1799964 was associated with ANM after adjustment for covariates (<i>β</i> = −1.020, <i>p</i><sub>perm</sub> = 0.035). All studied loci were associated with ANM after adjustment for breastfeeding (raw <i>p</i> The results of the present study suggest that the <i>TNF</i>, <i>LTA</i> and <i>TNFRSF1B</i> genes are associated with AM and ANM.
