Genetic and Environmental Correlations between Age at Menarche and Bone Mineral Density at Different Skeletal Sites

Low bone mineral density (BMD) is an important risk factor for osteoporotic fractures. Though previous studies have demonstrated that age at menarche (AAM) is phenotypically associated with BMD, the contributions of genetic and environmental factors to this association remain unknown. In this study, using variance decomposition analyses, we provided an accurate estimation of the genetic and environmental correlations between AAM and BMD in 2,667 Caucasian women from 512 pedigrees. After adjustment for significant covariates, we detected significant genetic correlations between AAM and BMD at the lumbar spine, femoral neck, and ultradistal radius (ρ _G = −0.1316, −0.1417, and −0.1137, respectively; all P < 0.01). However, all environmental correlations between AAM and BMD were nonsignificant (P > 0.05). We also generated a principal component factor for BMD (PC_BMD) and evaluated the relationship between this factor and AAM. The genetic and environmental correlations between PC_BMD and AAM (ρ _P = −0.0847, P < 0.001; ρ _G = −0.1737, P < 0.01; ρ _E = −0.0348, P > 0.05) were consistent with the results of BMD at the three skeletal sites and AAM. Our results confirmed the significant phenotypic association between BMD and AAM and for the first time suggested that this association is mainly attributable to shared genetic, rather than environmental, factors.