Mendelian Randomisation Study of Childhood BMI and Early Menarche
Mumby, Hannah S.
Elks, Cathy E.
Sharp, Stephen J.
Luben, Robert N.
Wareham, Nicholas J.
Loos, Ruth J. F.
Ong, Ken K.
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Mumby, H. S., Elks, C. E., Li, S., Sharp, S. J., Khaw, K., Luben, R. N., Wareham, N. J., et al. (2011). Mendelian Randomisation Study of Childhood BMI and Early Menarche. https://doi.org/10.1155/2011/180729
To infer the causal association between childhood BMI and age at menarche, we performed a mendelian randomisation analysis using twelve established “BMI-increasing” genetic variants as an instrumental variable (IV) for higher BMI. In 8,156 women of European descent from the EPIC-Norfolk cohort, height was measured at age 39–77 years; age at menarche was self-recalled, as was body weight at age 20 years, and BMI at 20 was calculated as a proxy for childhood BMI. DNA was genotyped for twelve BMI-associated common variants (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, MTCH2, SEC16B, FAIM2 and SH2B1), and for each individual a “BMI-increasing-allele-score” was calculated by summing the number of BMI-increasing alleles across all 12 loci. Using this BMI-increasing-allele-score as an instrumental variable for BMI, each 1 kg/ increase in childhood BMI was predicted to result in a 6.5% (95% CI: 4.6–8.5%) higher absolute risk of early menarche (before age 12 years). While mendelian randomisation analysis is dependent on a number of assumptions, our findings support a causal effect of BMI on early menarche and suggests that increasing prevalence of childhood obesity will lead to similar trends in the prevalence of early menarche.
External DOI: https://doi.org/10.1155/2011/180729
This record's URL: https://www.repository.cam.ac.uk/handle/1810/267571
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Rights Holder: Copyright © 2011 Hannah S. Mumby et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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