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Age at puberty and risk of asthma: A Mendelian randomisation study

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Title: Age at puberty and risk of asthma: A Mendelian randomisation study
Authors: Minelli, C
Amaral, AFS
Pereira, M
Jarvis, D
Potts, J
Item Type: Journal Article
Abstract: 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 provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide.
Issue Date: 7-Aug-2018
Date of Acceptance: 9-Jul-2018
URI: http://hdl.handle.net/10044/1/65417
DOI: 10.1371/journal.pmed.1002634
ISSN: 1549-1277
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS Medicine
Volume: 15
Issue: 8
Sponsor/Funder: National Heart & Lung Institute Foundation
Commission of the European Communities
Funder's Grant Number: 12PS6-14-17
633212
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
MULTIPLE GENETIC-VARIANTS
CAUSAL ODDS RATIOS
INSTRUMENTAL VARIABLES
OBSERVATIONAL EPIDEMIOLOGY
PROSPECTIVE COHORT
SEXUAL-MATURATION
SUMMARIZED DATA
MENARCHE
ASSOCIATIONS
MENOPAUSE
11 Medical And Health Sciences
Publication Status: Published
Open Access location: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002634
Article Number: e1002634
Appears in Collections:Infectious Disease Epidemiology
National Heart and Lung Institute
Faculty of Medicine



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