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Differential DNA methylation in monozygotic twins discordant for female sexual functioning

Burri, A1; Leupin, M2; Spector, T3; Marinova, Z4

1: Private Institute of Urology, Andrology and Sexual Medicine, Hamburg, Germany; 2: University of Zurich, Switzerland; 3: King's College London, United Kingdom; 4: Clinic Barmelweid, Barmelweid, Switzerland

Objective. Research has repeatedly pointed towards a multifactorial aetiology underlying female sexual dysfunction (FSD), in which genetic and environmental factors also play a role. As 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. The objective of this study was to identify differentially methylated CpG positions for sexual functioning in a sample of monozygotic (MZ) twin pairs discordant for sexual functioning.

Material and Methods. The sample consisted of 33 trait-discordant monozygotic twin pairs (age M 54.1 years, SD 9.05) from the TwinsUK 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. DNA methylation patterns associated with the FSFI-LL total score and its six subdomains were compared.

Results. Two differentially methylated CpG positions (cg09580409 and cg14734994) reaching experiment-wide statistical significance could be 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.

Conclusions. The present results provide a promising starting point to encourage further investigation of epigenetic mechanisms underlying sexual functioning and FSD. THNSL2 and SLC6A19, both of which have previously been linked to weight and adiposity, might represent novel candidates for sexual problems in women. Understanding how genes and environment interact to influence or sexuality may inform clinical practice and lead to new treatments for women experiencing FSD.


Work supported by industry: no, by NA (no industry support in study design or execution). The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry.

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