Candidate functional SNPs in regulatory and coding regions affect genes differently. Those occurring within the protein coding region can affect protein structure or lead to alternative splicing, potentially resulting in altered function or in some cases loss of function.35 Genetic variants located in non–coding regions often influence phenotypes by altering the expression of nearby genes (expression quantitative trait loci [eQTLs]).35 Genetic variants with evidence of colocalisation between variant associations and gene expression can be used to prioritise functional genes, although this method is limited by availability of gene expression datasets from tissues or cells relevant to the trait.35 Many, but not all, existing methods also assume there is only one functional variant in the locus.35 In addition to these in–silico approaches, candidate causal variants or genes should be experimentally validated in cell–based systems or model organisms to evaluate their biological function.32,35
