Age- and gender-dependent heterogeneous proportion of variation explained by SNPs in quantitative traits reflecting human health

Abstract

Age-related effects are often included as covariates in the analytical model for genome-wide association analysis of quantitative traits reflecting human health. Nevertheless, previous studies have hardly examined the effects of age on the proportion of variation explained by single nucleotide polymorphisms (PVSNP) in these traits. In this study, the PVSNP estimates of body mass index (BMI), waist-to-hip ratio, pulse pressure, high-density lipoprotein cholesterol level, triglyceride level (TG), low-density lipoprotein cholesterol level, and glucose level were obtained from Korean consortium metadata partitioned by gender or by age. Restricted maximum likelihood estimates of the PVSNP were obtained in a mixed model framework. Previous studies using pedigree data suggested possible differential heritability of certain traits with regard to gender, which we observed in our current study (BMI and TG; P<0.05). However, the PVSNP analysis based on age revealed that, with respect to every trait tested, individuals aged 40 to 49 exhibited significantly lower PVSNP estimates than individuals aged 50 to 59 or 60 to 69 (P<0.05). The consistent heterogeneous PVSNP with respect to age may be due to degenerated genetic functions in individuals between the ages of 50 and 69. Our results suggest the genetic mechanism of age-and gender-dependent PVSNP of quantitative traits related to human health should be further examined.