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Age at menarche and lung function: a Mendelian randomization study.

Gill, D; Sheehan, NA; Wielscher, M; Shrine, N; Amaral, AFS; Thompson, JR; Granell, R; Leynaert, B; Real, FG; Hall, IP; et al. Gill, D; Sheehan, NA; Wielscher, M; Shrine, N; Amaral, AFS; Thompson, JR; Granell, R; Leynaert, B; Real, FG; Hall, IP; Tobin, MD; Auvinen, J; Ring, SM; Jarvelin, M-R; Wain, LV; Henderson, J; Jarvis, D; Minelli, C (2017) Age at menarche and lung function: a Mendelian randomization study. Eur J Epidemiol, 32 (8). pp. 701-710. ISSN 1573-7284 https://doi.org/10.1007/s10654-017-0272-9
SGUL Authors: Gill, Dipender Preet Singh

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Abstract

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8-47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2-69.9; p = 0.001). In adolescent girls we found an opposite effect (-56.5 mL; -108.3 to -4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

Item Type: Article
Additional Information: © The Author(s) 2017. This article is an open access publication Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: FEV1/FVC, FVC, Lung function, Menarche, Mendelian randomization, Puberty, Adolescent, Adult, Airway Obstruction, Female, Forced Expiratory Volume, Genetic Variation, Humans, Lung, Menarche, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Predictive Value of Tests, Puberty, Random Allocation, Respiratory Function Tests, Sexual Maturation, Vital Capacity, Lung, Humans, Airway Obstruction, Respiratory Function Tests, Vital Capacity, Forced Expiratory Volume, Random Allocation, Predictive Value of Tests, Puberty, Menarche, Sexual Maturation, Polymorphism, Single Nucleotide, Adolescent, Adult, Female, Genetic Variation, Mendelian Randomization Analysis, 1117 Public Health and Health Services, Epidemiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Eur J Epidemiol
ISSN: 1573-7284
Language: eng
Dates:
DateEvent
August 2017Published
17 June 2017Published Online
7 June 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
R01 MH063706NIMH NIH HHSUNSPECIFIED
G1000861Medical Research CouncilUNSPECIFIED
G0501942Medical Research CouncilUNSPECIFIED
G0601361Medical Research CouncilUNSPECIFIED
MC_UU_12013/1Medical Research CouncilUNSPECIFIED
G0902125Medical Research CouncilUNSPECIFIED
UNSPECIFIEDWellcome TrustUNSPECIFIED
RL1 MH083268NIMH NIH HHSUNSPECIFIED
102215/2/13/2Wellcome TrustUNSPECIFIED
G1002319Medical Research CouncilUNSPECIFIED
R01 HL087679NHLBI NIH HHSUNSPECIFIED
R01 MH062633NIMH NIH HHSUNSPECIFIED
MR/N011317/1Medical Research CouncilUNSPECIFIED
633212Horizon 2020UNSPECIFIED
MC_PC_12010Medical Research CouncilUNSPECIFIED
MR/M022501/1Medical Research CouncilUNSPECIFIED
MC_PC_15018Medical Research CouncilUNSPECIFIED
G0500539Medical Research CouncilUNSPECIFIED
G0902313Medical Research CouncilUNSPECIFIED
G9815508Medical Research CouncilUNSPECIFIED
G0600705Medical Research CouncilUNSPECIFIED
PubMed ID: 28624884
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112799
Publisher's version: https://doi.org/10.1007/s10654-017-0272-9

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