A large replication study and meta-analysis in European samples provides further support for association of AHI1 markers with schizophrenia

Abstract

The Abelson helper integration site 1 (AHI1) gene locus on chromosome 6q23 is among a group of candidate loci for schizophrenia susceptibility that were initially identified by linkage followed by linkage disequilibrium mapping, and subsequent replication of the association in an independent sample. Here, we present results of a replication study of AHI1 locus markers, previously implicated in schizophrenia, in a large European sample (in total 3907 affected and 7429 controls). Furthermore, we perform a meta-analysis of the implicated markers in 4496 affected and 18,920 controls. Both the replication study of new samples and the meta-analysis show evidence for significant overrepresentation of all tested alleles in patients compared with controls (meta-analysis; P = 8.2 x 10(-5)-1.7 x 10(-3), common OR = 1.09-1.11). The region contains two genes, AHI1 and C6orf217, and both genes-as well as the neighbouring phosphodiesterase 7B (PDE7B)-may be considered candidates for involvement in the genetic aetiology of schizophrenia.

Figure 1.

The distribution of odds ratios across subgroups for five of the seven tested alleles at the AHI1 locus, along with the number of affected and control individuals for each subgroup, and the results of Woolf's test of homogeneity of odds ratios. Results for alleles rs7750586-A and rs9647635-A are not included as they are roughly equivalent to those for rs11154801-C.

Figure 2.

View of markers, genes and LD structure at the AHI1 locus using the UCSC Genome Browser (http://genome.ucsc.edu). The markers genotyped in different sub-samples to assess association of markers from the original family association study (9) are shown at top, followed by a track showing genes from the RefSeq database. Linkage disequilibrium (r²) in the HapMap CEU population (http://www.hapmap.org) is shown at bottom. Genomic coordinates are according to NCBI genome build 36.