The neuregulin 1 promoter polymorphism rs6994992 is not associated with chronic schizophrenia or neurocognition.
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.
Crowley
James J
JJ
Department of Genetics, University of North Carolina at Chapel Hill, North Carolina 27599-7264, USA. crowley@unc.edu
Keefe
Richard S E
RS
Perkins
Diana O
DO
Stroup
T Scott
TS
Lieberman
Jeffrey A
JA
Sullivan
Patrick F
PF
D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D020890:Neuregulin-1