Abstract

For more than a decade, genome-wide association studies have been applied to autoimmune diseases and have expanded our understanding on the pathogeneses. Genetic risk factors associated with diseases and traits are essentially causative. However, elucidation of the biological mechanism of disease from genetic factors is challenging. In fact, it is difficult to identify the causal variant among multiple variants located on the same haplotype or linkage disequilibrium block and thus the responsible biological genes remain elusive. Recently, multiple studies have revealed that the majority of risk variants locate in the non-coding region of the genome and they are the most likely to regulate gene expression such as quantitative trait loci. Enhancer, promoter and long non-coding RNA appear to be the main target mechanisms of the risk variants. In this review, we discuss functional genetics to challenge these puzzles.