University of Oulu

Gill, D., Sheehan, N.A., Wielscher, M. et al. Eur J Epidemiol (2017) 32: 701.

Age at menarche and lung function : a Mendelian randomization study

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Author: Gill, Dipender1,2; Sheehan, Nuala A.3; Wielscher, Matthias4;
Organizations: 1Department of Clinical Pharmacology and Therapeutics, Imperial College London, Hammersmith Hospital, London, UK
2St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK
3Department of Health Sciences, University of Leicester, Leicester, UK
4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
5Population Health and Occupational Disease, NHLI, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, SW3 6LR London, UK
6MRC-PHE Centre for Environment and Health, London, UK
7School of Social and Community Medicine, University of Bristol, Bristol, UK
8UMR 1152, Pathophysiology and Epidemiology of Respiratory Diseases, Epidemiology Team, Inserm, Paris, France
9UMR 1152, Univ Paris Diderot - Paris 7, Paris, France
10Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
11Department of Clinical Science, University of Bergen, Bergen, Norway
12Division of Respiratory Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham, UK
13National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK
14Institute of Health Sciences, University of Oulu, Oulu, Finland
15Biocenter Oulu, University of Oulu, Oulu, Finland
16Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland
17Unit of Primary Care, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link:
Language: English
Published: Springer Nature, 2017
Publish Date: 2019-05-09


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).

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Series: European journal of epidemiology
ISSN: 0393-2990
ISSN-E: 1573-7284
ISSN-L: 0393-2990
Volume: 32
Issue: 8
Pages: 701 - 710
DOI: 10.1007/s10654-017-0272-9
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
3141 Health care science
Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 633212. IPH was supported by an MRC programme Grant (G1000861). RG was supported by the UK Medical Research Council (Grant Ref: G0902125). The work of MDT, IPH and LVW was funded by a Medical Research Council (MRC) strategic award (MC_PC_12010). MDT was supported by MRC fellowships G0501942 and G0902313. This article presents independent research funded partially by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
Copyright information: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, 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.