The effect of early puberty on asthma in women and men: A Mendelian randomization study

Abstract

Evidence on whether early puberty increases the risk of adult asthma is suggestive but inconclusive in women, and very scarce in men. To overcome the issue of residual confounding in observational studies and provide evidence on casual effects, we used Mendelian randomization (MR) with 332 SNPs as instrumental variables for age at menarche in women, and 18 SNPs for age at voice breaking in men. Age at menarche was categorised as early ( 14), while age at voice breaking was recorded and analysed as at a younger, average or older age. Based on 243,316 women and 192,067 men from UK Biobank (9.2% and 6.3% with post-pubertal asthma, respectively), we find detrimental effects of early puberty on asthma. In women, an 8% increase in asthma risk for early and an 8% decrease for late menarche suggest a linear effect of pubertal timing. Similar effects are observed in males, even though the power is lower and the confidence intervals much wider (Figure). There is evidence of modest pleiotropy, but our findings are consistent across different methods robust to pleiotropy (Figure). We show detrimental effects of early puberty on asthma. As similar patterns are seen in both sexes, the effect in women is unlikely to be mediated by female sex hormones as hypothesised, suggesting instead a role of common (biological or psychological) factors related to early physical development. [ALEC, EU Grant #633212]