Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning

Background: Research has repeatedly suggested genetic and environmental factors in the etiology underlying female sexual dysfunction (FSD). Because sexual functioning is a highly variable trait, epigenetics could provide a promising approach to tackle the origins of FSD and consequently offer a step-change in our understanding of these problems. Aim: To identify differentially methylated CpG positions for sexual functioning in a sample of monozygotic twin pairs discordant for sexual functioning. Methods: The sample consisted of 33 trait-discordant monozygotic twin pairs (mean age = 54.1 years, SD = 9.05) from the Twins UK Registry. Phenotypic data on sexual desire, arousal, lubrication, orgasm, satisfaction, and pain were collected using the Female Sexual Function Index-Lifelong (FSFI-LL). The Illumina Infinium HumanMethylation 450 DNA BeadChip was used for epigenome-wide analyses of DNA methylation in whole-blood samples. Outcomes: Comparison of DNA methylation patterns associated with the FSFI-LL total score and its six subdomains. Results: Two differentially methylated CpG positions (cg09580409 and cg14734994) reaching experiment-wide statistical significance were found for overall sexual functioning, mapping to MGC45800 and the threonine synthase-like 2 gene (THNSL2), respectively. Furthermore, potential biologically relevant candidates for sexual desire (CUB and zona pellucida-like domains 1, CUZD1) and satisfaction (solute carrier family 6 member 19, SLC6A19) were identified. Clinical Translation: THNSL2 and SLC6A19, which have been linked to weight and adiposity, might represent novel candidates for sexual problems in women. Strengths and Limitations: This is the first study to investigate epigenetic mechanisms underlying FSD. The study used a relative small sample of monozygotic female twins. The cutoff to determine discordance in sexual problems was chosen based on a 10% FSFI score difference. Therefore, the results have to be interpreted with caution and need replication in larger clinical samples. Conclusion: Understanding how genes and environment interact to influence our sexuality might inform clinical practice and lead to new treatments for women experiencing FSD. Copyright (C) 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.