Validation of Osteoporosis associated SNPs candidates from Decisive Gene Strategy using Taiwan Biobank

Decisive gene strategy (DGS) has been developed and identified 21 single nucleotide polymorphisms (SNPs) associated with osteoporosis (OP). This study aimed to further evaluate whether DGS is a suitable candidate strategy to identify the relationship between SNPs and OP using Taiwan Biobank (TWB). A total of 26,225 samples were retrieved from TWB between 2008 and 2021, comprising 4,749 osteoporosis (T-score ≤ -2.5) and 21,476 controls (T-score ≥ -1.0) based on their T-score of bone mineral density (BMD). Logistic regression analysis was used to examine the association between 21 SNPs from DGS and OP risk by using TWB data. The alignment of 21 SNPs from DGS with TWB genotyping chip found 11 identical SNPs. Among the 11 identical SNPs, seven showed results consistent with prior DGS evidence, including ESR1 rs9340799, OPG rs2073617, VDR rs731236, rs7975232, and rs1544410, IL6 rs1800795, and IGF1 rs5742612 [OR: 1.01, 1.03, 1.06, 1.01, 1.10, 0.72, 1.02; 95% CI= 0.94-1.09, 0.97-1.10, 0.93-1.22, 0.94-1.07, 0.97-1.26, 0.32-1.64, 0.96-1.09, respectively]. Furthermore, OPG T245G rs3134069 showed a borderline nominal association with osteoporosis in TWB [OR: 1.09, 95% CI= 1.00-1.19]), suggesting a potential population-specific signal. Our TWB validation of the 11 identical SNPs supports DGS as an effective methodology and, beyond replication, provides a novel framework for examining the relationship between SNPs and disease.