Abstract
BACKGROUND: There are many research studies have estimated the heritability of phenotypic traits, but few have considered longitudinal changes in several phenotypic traits together. OBJECTIVE: To evaluate the progressive effect of single nucleotide polymorphisms (SNPs) on prominent health-related phenotypic traits by determining SNP-based heritability ([Formula: see text]) using longitudinal data. METHODS: Sixteen phenotypic traits associated with major health indices were observed biennially for 6843 individuals with 10-year follow-up in a Korean community-based cohort. Average SNP heritability and longitudinal changes in the total period were estimated using a two-stage model. Average and periodic differences for each subject were considered responses to estimate SNP heritability. Furthermore, a genome-wide association study (GWAS) was performed for significant SNPs. RESULTS: Each SNP heritability for the phenotypic mean of all sixteen traits through 6 periods (baseline and five follow-ups) were significant. Gradually, the forced vital capacity in one second (FEV1) reflected the only significant SNP heritability among longitudinal changes at a false discovery rate (FDR)-adjusted 0.05 significance level ([Formula: see text], FDR = 0.0012). On estimating chromosomal heritability, chromosome 2 displayed the highest heritability upon periodic changes in FEV1. SNPs including rs2272402 and rs7209788 displayed a genome-wide significant association with longitudinal changes in FEV1 (P = 1.22 × 10(-8) for rs2272402 and P = 3.36 × 10(-7) for rs7209788). De novo variants including rs4922117 (near LPL, P = 2.13 × 10(-15)) of log-transformed high-density lipoprotein (HDL) ratios and rs2335418 (near HMGCR, P = 3.2 [Formula: see text] 10(-9)) of low-density lipoprotein were detected on GWAS. CONCLUSION: Significant genetic effects on longitudinal changes in FEV1 among the middle-aged general population and chromosome 2 account for most of the genetic variance.