Imperial College London
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DrCosettaMinelli

Faculty of Medicine, National Heart & Lung Institute

Emeritus Reader in Medical Statistics
 
 
 
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cosetta.minelli1 Website

 
 
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Location

 

G 49Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gill:2018:10.1038/s41366-018-0048-7,
author = {Gill, DPS and Brewer, C and Del, Greco M F and Sivakumaran, P and Bowden, J and Sheehan, N and Minelli, C},
doi = {10.1038/s41366-018-0048-7},
journal = {International Journal of Obesity},
pages = {1574--1581},
title = {Age at menarche and adult body mass index: a Mendelian randomization study},
url = {http://dx.doi.org/10.1038/s41366-018-0048-7},
volume = {42},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundPubertal timing has psychological and physical sequelae. While observational studies have demonstrated an association between age at menarche and adult body mass index (BMI), confounding makes it difficult to infer causality.MethodsThe Mendelian randomization (MR) technique is not limited by traditional confounding and was used to investigate the presence of a causal effect of age at menarche on adult BMI. MR uses genetic variants as instruments under the assumption that they act on BMI only through age at menarche (no pleiotropy). Using a two-sample MR approach, heterogeneity between the MR estimates from individual instruments was used as a proxy for pleiotropy, with sensitivity analyses performed if detected. Genetic instruments and estimates of their association with age at menarche were obtained from a genome-wide association meta-analysis on 182,416 women. The genetic effects on adult BMI were estimated using data on 80,465 women from the UK Biobank. The presence of a causal effect of age at menarche on adult BMI was further investigated using data on 70,692 women from the GIANT Consortium.ResultsThere was evidence of pleiotropy among instruments. Using the UK Biobank data, after removing instruments associated with childhood BMI that were likely exerting pleiotropy, fixed-effect meta-analysis across instruments demonstrated that a 1 year increase in age at menarche reduces adult BMI by 0.38 kg/m2 (95% CI 0.25–0.51 kg/m2). However, evidence of pleiotropy remained. MR-Egger regression did not suggest directional bias, and similar estimates to the fixed-effect meta-analysis were obtained in sensitivity analyses when using a random-effect model, multivariable MR, MR-Egger regression, a weighted median estimator and a weighted mode-based estimator. The direction and significance of the causal effect were replicated using GIANT Consortium data.ConclusionMR provides evidence to support the hypothesis that earlier age at menarche causes
AU  - Gill,DPS
AU  - Brewer,C
AU  - Del,Greco M F
AU  - Sivakumaran,P
AU  - Bowden,J
AU  - Sheehan,N
AU  - Minelli,C
DO  - 10.1038/s41366-018-0048-7
EP  - 1581
PY  - 2018///
SN  - 0307-0565
SP  - 1574
TI  - Age at menarche and adult body mass index: a Mendelian randomization study
T2  - International Journal of Obesity
UR  - http://dx.doi.org/10.1038/s41366-018-0048-7
UR  - http://hdl.handle.net/10044/1/56300
VL  - 42
ER  -
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