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Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)(2)), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.

Original publication

DOI

10.1093/aje/kws473

Type

Journal article

Journal

American journal of epidemiology

Publication Date

08/2013

Volume

178

Pages

451 - 460

Addresses

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, 137 East Franklin Street, Suite 306, Campus Box 8050, Chapel Hill, NC 27514-8050, USA. fernandez-rhodes@unc.edu

Keywords

Humans, Obesity, Body Mass Index, Waist-Hip Ratio, Age Factors, Menarche, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Adolescent, Child, European Continental Ancestry Group, Women's Health, Female, Adiposity, Waist Circumference, Genetic Association Studies