biostudies-literatureUnknown53(2)Oginni OAOnly one study has examined bidirectional causality between sexual minority status (having same-sex attraction) and psychological distress. We combined twin and genomic data from 8700 to 9700 participants in the UK Twins Early Development Study cohort at ≈21 years to replicate and extend these bidirectional causal effects using separate unidirectional Mendelian Randomization-Direction of Causation models. We further modified these models to separately investigate sex differences, moderation by childhood factors (retrospectively-assessed early-life adversity and prospectively-assessed childhood gender nonconformity), and mediation by victimization. All analyses were carried out in OpenMx in R. Same-sex attraction causally influenced psychological distress with significant reverse causation (beta = 0.19 and 0.17; 95% CIs = 0.09, 0.29 and 0.08, 0.25 respectively) and no significant sex differences. The same-sex attraction → psychological distress causal path was partly mediated by victimization (12.5%) while the reverse causal path was attenuated by higher childhood gender nonconformity (moderation coefficient = -0.09, 95% CI: -0.13, -0.04).Behavior genetics118-131https://www.ebi.ac.uk/biostudies/studies/S-EPMC9922221biostudies-literatureBidirectional Causal Associations Between Same-Sex Attraction and Psychological Distress: Testing Moderation and Mediation Effects.PMC9922221Rahman QOginni OAEley TCLim KXRijsdijk FVJern PfalseBidirectional Causal Associations Between Same-Sex Attraction and Psychological Distress: Testing Moderation and Mediation Effects.Only one study has examined bidirectional causality between sexual minority status (having same-sex attraction) and psychological distress. We combined twin and genomic data from 8700 to 9700 participants in the UK Twins Early Development Study cohort at ≈21 years to replicate and extend these bidirectional causal effects using separate unidirectional Mendelian Randomization-Direction of Causation models. We further modified these models to separately investigate sex differences, moderation by childhood factors (retrospectively-assessed early-life adversity and prospectively-assessed childhood gender nonconformity), and mediation by victimization. All analyses were carried out in OpenMx in R. Same-sex attraction causally influenced psychological distress with significant reverse causation (beta = 0.19 and 0.17; 95% CIs = 0.09, 0.29 and 0.08, 0.25 respectively) and no significant sex differences. The same-sex attraction → psychological distress causal path was partly mediated by victimization (12.5%) while the reverse causal path was attenuated by higher childhood gender nonconformity (moderation coefficient = -0.09, 95% CI: -0.13, -0.04).2023-01-01T00:00:00Z2023 Mar2025-04-22T18:22:26.729Z2025-04-06T02:27:24.509ZS-EPMC99222213652024810.1007/s10519-022-10130-x