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@article{Minelli:2018:10.1371/journal.pmed.1002634,
author = {Minelli, C and van, der Plaat DA and Leynaert, B and Granell, R and Amaral, AFS and Pereira, M and Mahmoud, O and Potts, J and Sheehan, NA and Bowden, J and Thompson, J and Jarvis, D and Davey, Smith G and Henderson, J},
doi = {10.1371/journal.pmed.1002634},
journal = {PLoS Med},
title = {Age at puberty and risk of asthma: A Mendelian randomisation study.},
url = {http://dx.doi.org/10.1371/journal.pmed.1002634},
volume = {15},
year = {2018}
}

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TY  - JOUR
AB  - BACKGROUND: Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males. METHODS AND FINDINGS: MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (<12), normal (12-14), or late (>14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10(-5)) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10(-4)), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking. CONCLUSIONS: This large MR study prov
AU  - Minelli,C
AU  - van,der Plaat DA
AU  - Leynaert,B
AU  - Granell,R
AU  - Amaral,AFS
AU  - Pereira,M
AU  - Mahmoud,O
AU  - Potts,J
AU  - Sheehan,NA
AU  - Bowden,J
AU  - Thompson,J
AU  - Jarvis,D
AU  - Davey,Smith G
AU  - Henderson,J
DO  - 10.1371/journal.pmed.1002634
PY  - 2018///
TI  - Age at puberty and risk of asthma: A Mendelian randomisation study.
T2  - PLoS Med
UR  - http://dx.doi.org/10.1371/journal.pmed.1002634
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30086135
UR  - http://hdl.handle.net/10044/1/65417
VL  - 15
ER  -

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