If none of these tested SNPs and none of the other (not tested but known) SNPs in LD with the lead SNP are known to have a functional consequence (i.e., altering expression of a gene, affecting a binding site or violating the protein structure), no causal gene can be indicated. However, if one or several of the SNPs are known to affect the function of one of the genes in the area, but not the other genes, then that single gene has a higher probability of being functionally related to the disease. Pinpointing which and how genes are affected by SNPs associated with a trait is crucial in increasing our insight into the biological mechanisms underlying that trait. Interpreting SNP-trait associations requires adding functional information from several resources and repositories such as, e.g., the Genotype-Tissue Expression (GTEx)8, Encyclopedia of DNA Elements (ENCODE)9, Roadmap Epigenomics Project10, or chromatin interaction information11.
