Genotype-environment interactions for quantitative traits in Korea Associated Resource (KARE) cohorts

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Abstract

Background: Due to the lack of statistical power and confounding effects of population structure in human population data, genotype-environment interaction studies have not yielded promising results and have provided only limited knowledge for exploring how genotype and environmental factors interact to in their influence onto risk.Results: We analyzed 49 human quantitative traits in 7,170 unrelated Korean individuals on 326,262 autosomal single nucleotide polymorphisms (SNPs) collected from the KARE (Korean Association Resource) project, and we estimated the statistically significant proportion of variance that could be explained by genotype-area interactions in the supra-iliac skinfold thickness trait (hGE2 = 0.269 and P = 0.00032), which is related to abdominal obesity. Data suggested that the genotypes could have different effects on the phenotype (supra-iliac skinfold thickness) in different environmental settings (rural vs. urban areas). We then defined the genotype groups of individuals with similar genetic profiles based on the additive genetic relationships among individuals using SNPs. We observed the norms of reaction, and the differential phenotypic response of a genotype to a change in environmental exposure. Interestingly, we also found that the gene clusters responsible for cell-cell and cell-extracellular matrix interactions were enriched significantly for genotype-area interaction.Conclusions: This significant heritability estimate of genotype-environment interactions will lead to conceptual advances in our understanding of the mechanisms underlying genotype-environment interactions, and could be ultimately applied to personalized preventative treatments based on environmental exposures. © 2014 Kim et al.; licensee BioMed Central Ltd.

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Kim, J., Lee, T., Lee, H. J., & Kim, H. (2014). Genotype-environment interactions for quantitative traits in Korea Associated Resource (KARE) cohorts. BMC Genetics, 15. https://doi.org/10.1186/1471-2156-15-18

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