One problem is that GWAS hits identify variants, usually SNPs, that mark regions of the genome, so-called ‘loci’, but in most cases do not directly identify the genes themselves nor their causal alleles. A GWAS locus often includes multiple genes within the region of statistical significance, and a hit within a gene does not guarantee that that is the gene involved; the functional effect of the variants is not usually obvious, and it may even have a regulatory effect on a gene outside the GWAS risk locus. Data from large scale genomic and systems biology experiments are being used to identify expression, protein and methylation quantitative trait loci (e, p and m-QTLs) to try to better map causal alleles2122. This includes imputation of gene expression profiles2324. A caveat is that linkage disequilibrium between markers often results in multiple genes in a region being implicated by expression imputation, recapitulating the initial problem. In addition, the lack of large samples of available brain tissues from both patients and healthy donors at appropriate stages of development as yet hampers the wide scale application
