The genetic architecture of molecular traits

• Published in: Current opinion in systems biology 2017-02, Vol.1, p.25-31
• Main Authors: Claringbould, Annique, de Klein, Niek, Franke, Lude
• Format: Article
• Language: English
• ISSN: 2452-3100; 2452-3100
• DOI: 10.1016/j.coisb.2017.01.002

Most diseases have both an environmental and genetic component. Although many diseases are strongly heritable, individual genetic variants typically confer only a small effect on disease, and thus these diseases are strongly polygenic. Paradoxically, molecular traits, such as gene expression, methylation, protein or metabolite levels, typically have a lower heritability, but sometimes individual genetic variants show much higher effect sizes on these traits. In this review, we discuss the genetic architecture of these molecular traits, and contrast this to the genetic architecture of complex diseases, and provide explanations why strong effects of individual genetic variants on molecular traits do not necessarily need to translate into increased risk of disease. [Display omitted] •Effect sizes of SNPs on molecular traits are often much stronger than on disease.•Heritability of disease is usually higher than the heritability of molecular traits.•Distal QTLs have small effect sizes but are numerous, similar to complex diseases.•Large-scale QTL studies are needed to find the variants that alter molecular traits.