Heterogeneous genetic associations of nucleotide sequence variants with bone mineral density by gender

We examined genetic associations of previously identified sequence variants with bone mineral density and their heterogeneity by gender. Large-scale cohort data were used including a total of 8,419 subjects (4,034 males and 4,385 females) from the Korean Association REsource (KARE) cohort. Bone speed of sound (SOS) values were measured at distal radius or mid-shaft tibia by quantitative ultrasound. Genotypic associations of SOS were tested with each of nucleotide sequence variants identified by previous studies. The genetic association analysis revealed that 2 out of 11 nucleotide sequence variants were associated with SOS (rs1721400, rs7776725, P < 7.58 × 10−4). Further analysis with partitioning data by gender showed that the mid-shaft tibia phenotypes were associated with the rs1721400 and rs7776725 in females (P < 3.79 × 10−4), but not in males (P > 3.79 × 10−4). The current study suggested female-specific associations of rs1721400 and rs7776725 with bone mineral density and heterogeneity of genetic association by skeletal site measured for bone mineral density.