3.1 years ago by
UK, Hinxton, EMBL-EBI
I remember from a talk I gave with Daniel Zerbino that only 5.3% of variants from the GWAS catalog were located in coding sequences/splice sites. Intronic and intergenic variants accounted for 46% and 37%, respectively. In addition, non-coding regions can be extremely conserved across vertebrates and some of them can be bound by TF such as CEBPA.
So no wonder there is such hype on non-coding regions. They must (ought to) have an impact somehow. The 'how' is the tricky bit though.
There are many examples in the papers suggested by @Emily_Ensembl and @vchris_ngs, and the FTO is a classic one for me. FTO not only have an intronic variant associated with obesity, but the effect of this variant is not on the FTO, rather another gene.
For more on eQTL, functional genomics, LD, and assigning a variant (coding or otherwise) to a gene associated with a disease, check this paper out.