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KMID : 0381120200420040393
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Genes and Genomics
2020 Volume.42 No. 4 p.393 ~ p.403
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Progressive effects of single-nucleotide polymorphisms on 16 phenotypic traits based on longitudinal data
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Li Donghe
Kang Hahn
Lee Sang-Hun
Won Sung-Ho
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Abstract
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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 (h2snp) 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 (h2snp=0.171, 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 × 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.
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KEYWORD
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Heritability, Phenotypic trait, Genomic restricted maximum likelihood, Longitudinal changes
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