Assessing the genetic correlations between early growth parameters and bone mineral density: A polygenic risk score analysis

Objective: The relationships between early growth parameters and bone mineral density (BMD) remain elusive now. In this study, we performed a large scale polygenic risk score (PRS) analysis to evaluate the potential impact of early growth parameters on the variations of BMD. Methods: We used 2286 Caucasian subjects as cohort 1 and 3404 Framingham Heart Study (FHS) subjects as cohort 2 in this study. BMD at ulna & radius, hip and spine were measured using dual energy X-ray absorptiometry. BMD values were adjusted for age, sex, height and weight as covariates. Genome-wide single -nucleotide polymorphism (SNP) genotyping of the 2286 Caucasian subjects was performed using Affymetrix Human SNP Array 6.0. The GWAS datasets of early growth parameters were driven from the Early Growth Genetics Consortium, including birth weight (BW), birth head circumference (BHC), childhood body mass index (CBMI), pubertal height growth related indexes and tanner stage. Polygenic Risk Score (PRSice) and linkage disequilibrium (LD) score regression analysis were conducted to assess the genetic correlation between early growth parameters and BMD. Results: We detected significant genetic correlations in cohort 1, such as total spine BMD vs. CBMI (p value = 1.51 x 10(-4), rg = 0.4525), right ulna and radius BMD vs. CBMI (p value = 1.51 x 10(-4), rg = 0.4399) and total body BMD vs. tanner stage (p value = 7.00 x 10(-4), rg = - 0.0721). For cohort 2, significant correlations were observed for total spine BMD vs. height change standard deviation score (SDS) between 8 years and adult (denoted as PGF + PGM) (p value = 3.97 x 10(-4), rg = -0.1425), femoral neck BMD vs. the timing of peak height velocity by looking at the height change SDS between age 14 years and adult (denoted as PTF + PTM) (p value = 7.04 x 10(-4), rg = - 0.2185), and total spine BMD vs. PTF + PTM (p value = 6.86 x 10(-4), rg = - 0.2180). Conclusion: Our study results suggest that some early growth parameters could affect the variations of BMD.