ORIGINAL ARTICLE Genetic and environmental correlations between obesity phenotypes and age at menarche W Wang 1,2,5 , L-J Zhao 2,5 , Y-Z Liu 2 , RR Recker 2 and H-W Deng 1,3,4 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, Xi’an Jiaotong University, Xi’an, PR China; 2 Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE, USA; 3 School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA and 4 Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, PR China Objective: To assess the extent that the genetic and environmental factors contribute to the phenotypic correlations between obesity traits and age at menarche (AAM), and also to examine the influence of AAM on obesity in both pre- and postmenopausal women. Methods: Five hundred and twelve pedigrees with 2667 Caucasian female subjects from two to four generations were recruited. Fat mass and lean mass (both in kg) were measured by dual-energy X-ray absorptiometry scanner. Body mass index (BMI) (kg/m 2 ) was calculated. We performed bivariate quantitative genetic analyses in the total sample containing 2667 Caucasian women. We also selected 206 unrelated premenopausal women and 140 unrelated postmenopausal women from the total sample, and computed the respective phenotypic correlation between obesity and AAM in these two subgroups. Results: For fat mass, lean mass and BMI, we detected their significant negative genetic correlations with AAM after adjustment for significant covariates, which were 0.3170 (Po0.001), 0.1721 (Po0.05) and 0.3665 (Po0.001), respectively. However, their environmental correlations with AAM were all nonsignificant (P40.05), ranging from 0.0016 to 0.0192. In the premenopausal subgroup, significant associations were observed between fat mass and AAM (r ¼0.231, Po0.01) as well as between BMI and AAM (r ¼0.257, Po0.01). In the postmenopausal subgroup, no such associations were observed. Conclusion: Our results for the first time suggested that significant phenotypic association between obesity phenotypes and AAM is mainly attributable to shared genetic rather than environmental factors, and AAM may have stronger effects on obesity phenotypes in pre- than in postmenopausal women. International Journal of Obesity (2006) 30, 1595–1600. doi:10.1038/sj.ijo.0803322; published online 28 March 2006 Keywords: genetic correlation; environmental correlation; fat mass; lean mass; body mass index; age at menarche Introduction Menarche is an important developmental milestone in a female’s life. It signals the beginning of the ability to reproduce and is associated with the development of secondary sexual characteristics. Age at menarche (AAM) is an important anthropologic parameter for a female that may affect her health in her later life. A number of studies have suggested association between AAM and obesity pheno- types. 1–6 In a longitudinal study of the northern Finland birth cohort, the proportions of overweight and obese females were significantly higher in those who had earlier menarche. 3 Consistent with that, Wasserman et al. 6 found that early menarcheal ages (o12 years) were associated with the risk for obesity in postmenopausal women. Both obesity phenotypes and AAM are complex traits determined by multiple genetic and environmental factors, with genetic factors playing an important role. The narrow- sense heritability (h 2 ) was from 20 to 65% for fat mass, 7–9 from 52 to 77% for lean mass 9–11 and from 0.50 to 0.70 for body mass index (BMI). 11,12 Twin and family studies demonstrated that 46–72% of the variation in menarcheal age was attributed to genetic effects. 13–15 Although obesity and AAM are highly heritable and phenotypically correlated, it remains unclear whether and to what extent the phenotypic correlation between the two traits is due to shared genetic or shared environmental Received 25 July 2005; revised 16 February 2006; accepted 19 February 2006; published online 28 March 2006 Correspondence: Dr H-W Deng, School of Medicine, University of Missouri- Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA. E-mail: dengh@umkc.edu 5 These two authors contributed equally to this work. International Journal of Obesity (2006) 30, 1595–1600 & 2006 Nature Publishing Group All rights reserved 0307-0565/06 $30.00 www.nature.com/ijo