Genetics of human gene expression: mapping DNA variants that influence gene expression

Abstract

Expression levels of genes are heritable traits. Genetic determinants of individual variation in human gene expression can be mapped by linkage and association analyses. Cis- and trans-acting DNA variants influence expression levels of genes. Genetics of gene expression (GOGE) studies have identified cis-acting regulatory variants of many genes; however, few trans-acting variants have yet been identified. In humans, ∼30–50% of cis-acting variants identified in immortalized B cells have the same effects in other cell types, such as adipose tissue and blood. Differences in genotype frequencies of regulatory alleles contribute to population differences in gene expression. By combining results from GOGE studies with correlation analysis, one can construct directed gene co-expression networks that provide information on causal rather than just correlative relationships. The results also extend regulatory relationships from pairs to groups of genes. GOGE studies in cells exposed to cellular, medical or environmental perturbations will uncover additional regulators of human gene expression.