Integrated in-depth bioinformatic analysis suggests RELCH/KIAA1468, LINC02341, and AKAP11 as candidate genes for ages at menarche and menopause
Background: Polymorphisms of the TNFRSF11A and TNFSF11 genes were reported for their association with age at menarche (AAM) and age at natural menopause (ANM). However, the biological mechanisms underlying this association remain largely unclear. The aim of the study: This study was to determine biological processes backing the observed genetic associations. Materials and methods: Forty-four SNPs were analyzed using in silico approach and ten publicly available online databases and tools. Results:TNFRSF11A and TNFSF11 are highly pleiotropic genes that play a role in many metabolic processes. However, among that variety, lipid metabolism and cell survival and apoptosis seem the most biologically plausible mechanisms, through which these genes contribute to AAM and ANM. The analysis identified several mechanisms underlying the previously determined association of the TNFRSF11A and TNFSF11 genes with AAM and ANM and suggested RELCH/KIAA1468, LINC02341, and AKAP11as new candidate genes for the traits. Conclusion: The in silico analysis is a powerful approach making it possible to uncover possible metabolic pathways underlying observed genetic associations.