Making Sense of GWAS: Integrating Genetic Variation with Gene Expression to Derive Functional Mechanisms Underlying Disease Risk
Genome-wide association studies (GWAS) have made enormous strides in identifying common genetic variants that contribute to common diseases1, 2 and disease-associated traits3. Most of these genetic variants occur in non-coding sequences within introns of genes or in regions of the genome between genes, so called gene deserts, suggesting that they affect gene expression and regulation rather than the sequence of the expressed proteins. Genetic variants don't just affect gene expression in their vicinity but can affect gene expression on different chromosomes. This reflects the finite geometry of the genome within the nucleus, where transcription factor complexes serve multiple active templates. Thus, a variant that disrupts gene expression by affecting the recruitment of transcription factors on one chromosome can also have a strong effect at genes on other chromosomes.
- Received December 15, 2014.
- Accepted December 18, 2014.