Shedding new light on genetic dark matter

Discoveries from genome-wide association studies have contributed to our knowledge of the genetic etiology of many complex diseases. However, these account for only a small fraction of each disease's heritability. Here, we comment on approaches currently available to uncover more of the genetic 'dark matter,' including an approach introduced recently by Naukkarinen and colleagues. These authors propose a method for distinguishing between gene expression driven by genetic variation and that driven by non-genetic factors. This dichotomy allows investigators to focus statistical tests and further molecular analyses on a smaller set of genes, thereby discovering new genetic variation affecting risk for disease. We need more methods like this one if we are to shed a powerful light on dark matter. By enhancing our understanding of molecular genetic etiology, such methods will help us to understand disease processes better and will advance the promise of personalized medicine.