SNPs may occur within protein-coding sequences, introns, regulatory regions, or between genes. Missense variants or other alterations of coding sequences can have profound effects on protein function. For example, linkage analysis of cystic fibrosis inheritance in families has identified multiple mutations in CFTR (cystic fibrosis transmembrane conductance regulator), with the most common variant resulting in the deletion of a phenylalanine (Kerem et al., 1989). Some SNPs reside in the coding region but do not change the amino acid sequence (i.e., synonymous) whereas others are found in non-coding regions, as is the case for many common variants associated with AUD (Clarke et al., 2011, 2017; Zuo et al., 2014). Here, the functional consequence of a disease-associated SNP is more difficult to assess and could result in a change in the expression level of a disease-relevant protein or a change in splicing/regulation of a transcript. Such SNPs may constitute expression quantitative trait loci (eQTLs), which have profound effects on transcript abundance. However, association of a SNP with a phenotype does not necessitate that the SNP plays a causal role; this may be
