Rs7527939

rs7527939 is a C/T polymorphism located in the second intronic region of the hedgehog acyltransferase gene (HHAT), located on human chromosome 1 1. HHAT, also known as SKI1, is responsible for an enzyme that catalyzes amino-terminal palmitoylation 2 of hedgehog (SHH) through the secretory pathway 3,. According to dbSNP, the ancestral allele is C, and the minor allele frequency from the 1000 Genomes Project is 26.6% 1. Population-specific allele frequencies from the International HapMap Project are given below in graphic form.

A GWAS found a significant association between rs7527939 and a diagnosis of schizophrenia or schizoaffective disorder in a Bulgarian population. Using 188 affected and 376 unaffected individuals, the study tested 554, 496 SNPs for association with schizophrenia. After this initial test, the 100 SNPs with the lowest p-values were re-genotyped and re-tested for significance in a validation set of 99 cases and 328 controls. None of the SNPs were significant in this validation study, but combined with the initial analysis, rs7527939 showed a significant association, with a p-value of 6.49E-9. The odds ratio for the major allele was found be 2.63 with a 95% confidence interval of 1.89-3.66.

The results of this study have not been validated by any other studies, as this is the only paper that has been published on this SNP.

While the understanding of the cause of schizophrenia is still not very well understood, it is hypothesized that the disease may stem from compromised neuronal network development during development, which leads to increased vulnerability to environmental stresses. The authors state that disruption of the SHH gene, which interacts with HHAT, may cause errors in neuronal cell migration and interaction during development, possibly leading to schizophrenia or schizoaffective disorder. Overall, this study may shed some light on the cause of schizophrenia, and provides preliminary evidence that rs7527939 might be added to the growing list of SNPs associated with schizophrenia.


 * is_associated_with_disease::Schizophrenia
 * is_associated_with_disease::Schizoaffective disorder