Genetic effects are often compartmentalized--spatially, temporally and contextually
A eLife paper reports a special category of eQTLs called dynamic eQTLs or context-specific eQTLs. The authors demonstrate that certain genetic variants influence gene expression only under specific environmental conditions. By differentiating iPSCs into cardiomyocytes, and inducing hypoxia, the authors simulate the hypoxic state that the heart cells of a living individual experience after a myocardial infarction. While some eQTLs are expressed both in normoxic and hypoxic conditions, interestingly, some are expressed only either in normoxic or hypoxic conditions.
This phenomenon of compartmentalization of genetic effects is often ignored by the GWAS community. People often see genetic variations as constant variables present from birth till death, which is obvioulsly wrong. Although the genetic variants are present in the DNA of every cell in our body since birth to death, they become functional only at specific time points, at specific locations and at specific circumstances. Here the authors demonstrate the dynamic nature of genetic variations using gene expression as a phenotype. But this can easily apply to any GWAS phenotypes, for example, cognition. That’s why results from GWASs of intelligence in children and adults can differ. Similarly, GWASs of intelligence in typically developing adolescents and adolescents who are at their prodromal stage of schizophrenia can differ. As the resolution of the biobank phenotypes become better and better, such fascinating differences will unfold themselves.