From genomic advances to public health benefits: the unbearable lightness of being stuck

Abstract

Genetic determinants of common human diseases are still poorly understood. Due to large investments, many small successes have been made and the research field is rapidly expanding. However, genetic susceptibility variants showing repeatable associations with common diseases are usually of small effect. They are therefore unlikely to individually explain substantial share of disease burden in any community or provide new insights into disease pathogenesis that could lead to development of new drugs effective in considerable portion of the disease cases in a population. Genetic architecture of common diseases is beginning to reveal an incredible diversity of potential genetic causes that act through somewhat limited number of mechanisms with important contribution of environmental interactions. In light of these findings, we present current understanding of genetic architecture of a spectrum of human diseases. We address the encountered problems in susceptibility gene identification, review the success of leading gene identification strategies and discuss current prospects for translating genomic advances into measurable public health benefits.