Assessing the Genetic Correlations Between Blood Plasma Proteins and Osteoporosis: A Polygenic Risk Score Analysis

Osteoporosis is a common metabolic bone disease. The impact of global blood plasma proteins on the risk of osteoporosis remains elusive now. We performed a large-scale polygenic risk score (PRS) analysis to evaluate the potential effects of blood plasma proteins on the development of osteoporosis in 2286 Caucasians, including 558 males and 1728 females. Bone mineral density (BMD) and bone areas at ulna & radius, hip, and spine were measured using Hologic 4500W DXA. BMD/bone areas values were adjusted for age, sex, height, and weight as covariates. Genome-wide SNP genotyping of 2286 Caucasian subjects was performed using Affymetrix Human SNP Array 6.0. The 267 blood plasma proteins-associated SNP loci and their genetic effects were obtained from recently published genome-wide association study (GWAS) using a highly multiplexed aptamer-based affinity proteomics platform. The polygenetic risk score (PRS) of study subjects for each blood plasma protein was calculated from the genotypes data of the 2286 Caucasian subjects by PLINK software. Pearson correlation analysis of individual PRS values and BMD/bone area value was performed using R. Additionally, gender-specific analysis also was performed by Pearson correlation analysis. 267 blood plasma proteins were analyzed in this study. For BMD, we observed association signals between 41 proteins and BMD, mainly including whole body total BMD versus Factor H (p value = 9.00 × 10^-3), whole body total BMD versus BGH3 (p value = 1.40 × 10^-2), spine total BMD versus IGF-I (p value = 2.15 × 10^-2), and spine total BMD versus SAP (p value = 3.90 × 10^-2). As for bone areas, association evidence was observed between 45 blood plasma proteins and bone areas, such as ferritin versus spine area (p value = 1.90 × 10^-2), C4 versus hip area (p value = 1.25 × 10^-2), and hemoglobin versus right ulna and radius area (p value = 2.70 × 10^-2). Our study results suggest the modest impact of blood plasma proteins on the variations of BMD/bone areas, and identify several candidate blood plasma proteins for osteoporosis.