Results
The mean age of the study subjects was 49.57 years, with BMI values between 16.58 kg/m2 and 37.27 kg/m2. We examined distribution patterns of three BMD phenotypes: LS-BMD, FN-BMD, and FT-BMD. LS-BMD ranged between 0.78 g/cm2 and 1.84 g/cm2 (mean ± SD, 1.21 ± 0.38 g/cm2), FN-BMD ranged between 0.64 g/cm2 and 1.93 g/cm2 (mean ± SD, 0.98 ± 0.14 g/cm2), and FT-BMD ranged between 0.29 g/cm2 and 1.93 g/cm2 (mean ± SD, 1.04 ± 0.14 g/cm2) (Table 1). We identified five SNPs with a significant influence on BMD. Rs17124500 (p = 6.42 × 10-7), rs34594869 (p = 6.53 × 10-7), rs17124504 (p = 6.53 × 10-7), and rs140155614 (p = 8.64 × 10-7) were significantly associated with LS-BMD, and rs111822233 (p = 6.35 × 10-7) was associated with FT-BMD (Table 2). Fig. 1 illustrates regional plots of the five significant SNPs within 200 kilobytes. No genomic association between FN-BMD and any polymorphic nucleotides was established. Quantile–quantile and Manhattan plots of the p-values are shown in Supplementary Figs. 1 and 2.
Examination of genomic location revealed that rs17124500, which was the polymorphic nucleotide most closely associated with LS-BMD, is generally detected in potassium channel, subfamily K, member 1 (KCNK10) in 14q31.3 (Fig. 1A). Rs34594869 and rs17124504, were observed upstream of regions with high linkage disequilibrium constants, defined here as D' >0.8. Rs140155614 was most prominent in the aminoglycoside phosphotransferase domain containing 1 (AGPHD1) locus 15q25.1 (Fig. 1B). All four of these SNPs occurred as intron variants. rs111822233, the only sequence to influence the mineral density of the femur total, was positioned around the nuclear receptor subfamily 3, group C, member 2 (NR3C2) in 4q31.1 (Fig. 1C). The function of this SNP is currently undetermined.
In addition to establishing links between genetic polymorphisms and BMD, our studies aimed to identify loci previously confirmed as osteoporosis factors in Korean male populations in order to verify our outcomes (Table 3). Rs61382873 in LRP5 exhibited the highest association with LS-BMD (p = 0.0009). Rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were also linked to the lumbar spine region, albeit with higher p-values. Patterns of rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were correlated with FT-BMD, while rs61769193 (p = 0.0114) in ZBTB was found to influence FN-BMD.