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. Burri A, Leupin M, Spector T, Marinova Z. Differential DNA Methylation in Monozygotic Twins Discordant for Female Sexual Functioning. J Sex Med 2017;14:1357-1364.

A multivariate twin study of female sexual dysfunction.

INTRODUCTION: There is little work on the etiology of female sexual dysfunction (FSD), a highly contentious and heterogeneous disorder from classification and clinical perspectives. Clarifying causative mechanisms may enhance current psychiatric nosology. AIM: To elucidate the structure of genetic and environmental risk factors underlying the major subtypes of FSD. METHODS: Self-report questionnaires and multivariate twin model fitting on a population-based adult twin register (TwinsUK, London) including 1,489 female twins aged 18 to 85, comprising 244 MZ pairs, 189 DZ pairs, and 623 women whose co-twins did not participate. MAIN OUTCOME MEASURES: Scores on the Female Sexual Function Index-Lifelong and its six dimensions (desire, arousal, lubrication, orgasm, satisfaction, and pain) were subject to univariate and multivariate variance component analysis. RESULTS: The best-fitting multivariate model was an ACE Cholesky model, in which both additive genetic effects and non-shared environmental effects loaded on four FSD dimensions. There was significant genetic sharing between desire, arousal, lubrication and orgasm, but there was also significant genetic sharing between arousal, lubrication and orgasm independent of desire. These genetic loadings were small to modest effects (7% to 33%). Bivariate heritabilities suggested that a third of the covariance between these dimensions was genetic. Desire shared the least amount of genetic association with lubrication and orgasm. Non-shared environmental effects (which were stronger than genetic effects) were somewhat more dimension-specific. CONCLUSIONS: FSD is not etiologically homogeneous. There are at least two genetic factors to FSD symptomatology, and a tendency for more dimension-specific non-shared environmental factors as a more important indicative of unique factors involved in specific types of sexual problems reported by women. These results emphasize genetic factors as possible organizing principles for an etiologically based classification approach of FSD.