“…Several of these PrCa risk loci contain genes heavily linked to prostate function, or whose expression is enriched in the prostate relative to other tissues [ 195 ]; however, the biological mechanisms underpinning the majority of PrCa risk loci identified through GWAS generally remain poorly characterised at present. Functional validation of a small number of candidate causal variants has been performed to date [ 169 , 175 , 178 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 ], whilst fine-mapping of association signals and in silico annotation procedures have also helped to narrow the pool of likely candidate causal variants and identify prospective target genes and biological mechanisms that may give rise to differential risk [ 173 , 206 , 207 , 208 , 209 ]. A related methodology, transcriptome wide association studies (TWAS), in which GWAS summary statistic datasets and SNP-gene expression data from a reference panel are integrated, for the purpose of imputing gene expression data into phenotyped datasets which lack directly measured expression data, has also been employed in order to identify prospective gene–trait associations and prioritise putative candidate genes at many GWAS loci [ 210 ].…”