Shared genetic etiology of age of menarche and sosocioeconomic variables: No evidence for geneticoverlap with psychiatric traits

Earlier research has shown observational associations of earlypubertal timing and poor mental health. Mendelian randomization (MR)studies demonstrated a transient effect of pubertal timing on mentalhealth during adolescence, but not later in life. MR studies also showedthat there is a likely causal association of pubertal timing with life historytraits. However, the strongest causal effects and genetic correlations withage of menarche have been found for Body Mass Index (BMI). As highBMI is associated with lower socioeconomic status and with poor mentalhealth, the shared genetic etiology of socioeconomic status, BMI andpoor mental health is not yet fully understood. BMI correlates negativelywith socioeconomic status and several mental health outcomes. Despitetheir substantial genetic overlap, the underlying genetic etiology of thesephenotypes remains unclear. In this study we applied Linkage Disequi-librium score regression to test genetic correlations of age of menarchewith 33 socioeconomic, life history, social interaction, personality andpsychiatric traits, and BMI. We further applied spectral decompositionand hierarchical clustering to the genetic correlation matrix. After con-trolling for multiple testing, we could only identify significant geneticcorrelations with BMI and three socioeconomic traits (household income,deprivation and parental longevity). The results suggest that genome-wide association studies on age of menarche also contain socioeconomicinformation. Future MR studies aiming to test the unconfounded effectof pubertal timing should make sure that genetic instruments have nopleiotropic effect on socioeconomic variables, or (if possible) also controlfor socioeconomic status on the observational level.