The focused analysis of variants in the chromosome 9p21.2 locus, which was previously associated with ALS [7], [12], did not identify rs2814707 or rs3849942 as eQTL SNPs. We did, however, find evidence of two other SNPs (rs10122902 and rs1565948), located within a large LD block surrounding the previously associated markers, to be correlated with altered expression levels of C9orf72 isoform a. SNP rs1565948 was associated with ALS in our joint GWAS data. The rs10122902 variant was not associated with ALS in our joint GWAS, but was previously shown to be part of a haplotype with rs3849942, in which the major allele of rs10122902 was associated with increased risk of ALS [12]. Genetic variation in the chromosome 9p21.2 locus, therefore, appears to be associated with altered gene expression of C9orf72. The recent discovery of the intronic hexanucleotide repeat expansion in C9orf72 on a common haplotype in 9p21.2 linked families with ALS and FTD [15], [16], [47] thus illustrates the potential of the combined use of gene expression and genotyping in search for causative genes in human diseases. The mechanism though of
