Mining GWAS mountains for missing heritability

What is missing? The catchy term “missing heritability” refers to a long-standing issue in human genetics that is particularly relevant to common diseases that are thought to have complex genetic architecture. Even though we know several thousands of risk factors for common diseases, the sum of all these risk factors only explains a small proportion of the genetic risk for disease. Where is all the remaining genetic disease risk hidden? A recent publication in PLOS Genetics suggests that known association peaks in genome-wide association studies (GWAS) may harbor more than one risk variant, turning GWAS peaks into mountain ranges. Also, this publication provides an interesting state-of-the art review on the role of common and rare variants with respect to missing heritability. Let’s turn back the clock and start with the decade-old debate on common versus rare variant models of human disease. Continue reading