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.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

“…In contrast, without prediabetes, it is suspected that older individuals might exhibit a greater genetic susceptibility to CVD than younger individuals. This speculation aligns with a previous study conducted in our laboratory, indicating that the elderly population tends to display higher heritability for complex human traits[ 2 ]. However, it should not be overlooked that there are notable differences between this heritability study[ 2 ] and the study of Xie et al [ 1 ].…”

“…This speculation aligns with a previous study conducted in our laboratory, indicating that the elderly population tends to display higher heritability for complex human traits[ 2 ]. However, it should not be overlooked that there are notable differences between this heritability study[ 2 ] and the study of Xie et al [ 1 ]. For instance, the heritability study was conducted using a Korean population and did not analyze susceptibility to CVD, although critical risk factors such as body mass index[ 3 - 5 ], low-density lipoprotein cholesterol[ 6 - 8 ], and pulse pressure[ 9 - 11 ] were considered.…”

Genome-Wide Expression Quantitative Trait Loci Analysis Using Mixed Models

“…Of course, the specified analyses can be extended to the identification of any other potential heterogeneity in eQTLs. An example is age-dependent eQTLs, which may explain the heterogeneous heritability of complex phenotypes by age ( Lee and Lee, 2015 ). Thus, employing a mixed model should be emphasized to reduce spurious eQTLs in genome-wide eQTL analyses.…”

Analytical Models For Genetics of Human Traits Influenced By Sex

“…However, the homogeneity problem cannot be overcome by this approach for many sex-influenced traits. For example, heritability (a portion of phenotypic variance explained by genetic effects) of men was larger than that of women for body mass index and triglyceride level [ 10 ]. This heterogeneous heritability must be attributed to difference in individual genetic effects between women and men.…”