The association of calcium signaling pathway gene variants, bone mineral density (BMD) and mild cognitive impairment (MCI) is poorly understood so far. A total of 878 participants from Qingdao city were recruited in this study. According to the candidate gene selection method, 58 single nucleotide polymorphisms (SNPs) in eight calcium signaling genes were selected. The association between gene polymorphisms and MCI was revealed by using multiple genetic models. Polygenic risk scores (PRS) were used to summarize the effects of the whole gene. Logistic regression was used to analyze the association between each PRS and MCI. The multiplicative interaction term in the regression models was used to estimate the interaction effects between the PRS and BMD. We observed significant associations of rs6877893 (NR3C1), rs6448456 (CCKAR), and rs723672 (CACNA1C) polymorphisms with MCI. The PRSs of NR3C1 (OR = 4.012, 95% CI = 1.722-9.347, p < 0.001), PRKCA (OR = 1.414, 95% CI = 1.083-1.845, p = 0.011) and TRPM1 (OR = 3.253, 95% CI = 1.116-9.484, p = 0.031) were associated with an increased risk of developing MCI, and the PRS of total genes (OR = 0.330, 95% CI = 0.224-0.485, p < 0.001) was associated with a decreased risk of developing MCI. In interaction effect analysis, the interaction effect of PRKCA and BMD was significant. Genetic variations of the calcium signaling pathway were associated with MCI in older people. There was an interaction effect between PRKCA gene variants and BMD on MCI.
Keywords: bone mineral density; calcium signaling pathway; interaction effect; mild cognitive impairment; polygenic risk scores.