The neuregulin 1 promoter polymorphism rs6994992 is not associated with chronic schizophrenia or neurocognition

Abstract

The neuregulin 1 (NRG1) promoter single nucleotide polymorphism (SNP) rs6994992 has shown association with decreased activation of frontal and temporal lobe regions, increased risk of psychosis, and decreased premorbid IQ. This SNP is part of a putative schizophrenia risk-associated haplotype and was associated with increased expression of the type IV transcript in postmortem tissue. We tested for association between rs6994992 and chronic schizophrenia by genotyping 738 cases from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and 733 matched controls. We further tested for associations with age at onset and baseline neurocognition in cases with schizophrenia reasoning that these phenotypes might yield results similar to those seen for premorbid IQ. Affection status was weakly associated with rs6994992 genotypes and trended towards association under a recessive model. This association did not survive correction for multiple comparisons and was in the opposite direction than has been reported. There was no association between rs6994992 and age at onset, an estimate of premorbid IQ, or neurocognition at study baseline. We were unable to replicate previous associations of rs6994992 with schizophrenia and, moreover, did not find significant associations with age of onset, an estimate of pre-morbid IQ, or neurocognition.

Association study of Neuregulin-1 gene polymorphisms in a north Indian schizophrenia sample

“…The associations between rs35753505 and rs6994992 and cognitive functions noted here are consistent with prior reports in Caucasian samples; e.g., (Yokley et al, 2012) and (O’Tuathaigh et al, 2007), though there are some reports of non-significant associations (Crowley et al, 2008). In healthy participants, rs35753505 was not associated with working memory or task performance (Krug et al, 2008; Kircher et al, 2009a), but was associated with semantic verbal fluency (Kircher et al, 2009b) and sustained attention (Stefanis et al, 2007).…”

Genomewide association for schizophrenia in the CATIE study: results of stage 1

“…The SNP rs6994992 84,85 was not genotyped in this GWAS but had been done in these samples previously: rs6994992 was weakly associated with SCZ but in the opposite direction than has been reported. 86 Of the 13 SNPs in the vicinity of COMT, 2 consecutive exonic SNPs, 1 kb apart, had P = 0.02. These were rs4633 (synonymous) and rs4680 (val158-met), which has been widely studied as a genetic risk factor for SCZ and other disorders.…”

Neuregulin 1–erbB4 pathway in schizophrenia: From genes to an interactome

“…The same allele was also associated with changes in spatial working memory capacity in healthy control male subjects [65]. However, in another cohort of patients with chronic schizophrenia, SNP8NRG243177 was not associated with either schizophrenia, age of onset or neurocognition [66]. …”