Association of Adiposity Genetic Variants With Menarche Timing in 92,105 Women of European Descent

Lindsay Fernandez-Rhodes*, Ellen W. Demerath, Diana L. Cousminer, Ran Tao, Jill G. Dreyfus, Tonu Esko, Albert V. Smith, Vilmundur Gudnason, Tamara B. Harris, Lenore Launer, Patrick F. McArdle, Laura M. Yerges-Armstrong, Cathy E. Elks, David P. Strachan, Zoltan Kutalik, Peter Vollenweider, Bjarke Feenstra, Heather A. Boyd, Andres Metspalu, Evelin MihailovLinda Broer, M. Carola Zillikens, Ben Oostra, Cornelia M. van Duijn, Kathryn L. Lunetta, John R. B. Perry, Anna Murray, Daniel L. Koller, Dongbing Lai, Tanguy Corre, Daniela Toniolo, Eva Albrecht, Doris Stoeckl, Harald Grallert, Christian Gieger, Caroline Hayward, Ozren Polasek, Igor Rudan, James F. Wilson, Chunyan He, Peter Kraft, Frank B. Hu, David J. Hunter, Jouke-Jan Hottenga, Gonneke Willemsen, Dorret I. Boomsma, Enda M. Byrne, Nicholas G. Martin, Grant W. Montgomery, Nicole M. Warrington, Craig E. Pennell, Lisette Stolk, Jenny A. Visser, Albert Hofman, Andre G. Uitterlinden, Fernando Rivadeneira, Peng Lin, Sherri L. Fisher, Laura J. Bierut, Laura Crisponi, Eleonora Porcu, Massimo Mangino, Guangju Zhai, Tim D. Spector, Julie E. Buring, Lynda M. Rose, Paul M. Ridker, Charles Poole, Joel N. Hirschhorn, Joanne M. Murabito, Daniel I. Chasman, Elisabeth Widen, Kari E. North, Ken K. Ong, Nora Franceschini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


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 (19702010), 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 917 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 languageEnglish
Article numberN/A
Pages (from-to)451-460
Number of pages10
JournalAmerican Journal of Epidemiology
Issue number3
Publication statusPublished - 1 Aug 2013


  • adiposity
  • body mass index
  • genetic association studies
  • menarche
  • obesity
  • waist circumference
  • waist:hip ratio
  • womens health
  • AGE
  • LOCI
  • RISK


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