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Chunk #45 — Discussion

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Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.
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Detailed tagging analysis of the ZNF804A locus based upon HapMap SNPs did not identify any variants that were more strongly associated in the Cardiff Full sample or in fatSNP2. Addressing the possibility that there exists a common variant that might be more strongly associated than rs1344706, but that is not present in the HapMap, we undertook sequencing across most of the genomic region. Although this uncovered a number of additional variants not present in the HapMap, these additional SNPs were well covered by the existing genotyped SNPs. Despite the fact that the vast majority (99%) of all the known variation across ZNF804A could be imputed and/or tagged at least at r2>0.9, no additional markers were more strongly associated than rs1344706. Moreover, few markers were even moderately correlated with rs1344706. In supplemental table 11, we list all markers with r2>0.2 in relation to rs1344706 and their imputed p values. If rs1344706 was only weakly or moderately correlated with a true susceptibility variant, we would expect the association signal at that second SNP to be considerably stronger than observed at rs1344706. The