Study Report

Reference	Walker, R. M.,2010 PMID: 20435087
Citation	Walker, R. M., A. Christoforou, et al. (2010). "Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder." Neurosci Lett 478(1): 9-13.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	307 control, 303 SCZ, and 239 BPD subjects in the Scottish 2 sample,397 control, 396 SCZ, and 400 BPD subjects in the German sample
SNP/Region/Marker Size	5 SNPs
Predominant Ethnicity	Caucasian
Population	Scottish and German

Sample Diagnosis	DSM
Sample Status	The Scottish 1 case-control sample has been described previously. For the Scottish 2 sample, individuals diagnosed with BPD or SCZ were recruited from inpatient and outpatient services at psychiatric hospitals in South-East and South-Central Scotland, and from Ravenscraig Hospital, Greenock, Inverclyde. Control subjects in the Scottish 2 sample were recruited from the same population in South-East and South-Central Scotland and from the Grampian region of Scotland, with the majority (>80%) recruited through the Scottish National Blood Transfusion Service, which only accepts individuals who are not currently taking medication and do not have a chronic illness.The German case-control sample comprised individuals with a lifetime diagnosis of BPD or SCZ, according to DSM-IV criteria, who were recruited from consecutive admissions to the inpatient unit of the Department of Psychiatry and Psychotherapy of the University of Bonn and of the Central Institute of Mental Health in Mannheim.German control subjects were recruited from the Bonn region of Germany. Both the patient and the control samples were of German ancestry, extending back at least three generations.Following these quality control measures, genotype data was available for five SNPs (three region A SNPs and two region B SNPs) in 307 control, 303 SCZ, and 239 BPD subjects in the Scottish 2 sample, and for the three region B SNPs in 397 control, 396 SCZ, and 400 BPD subjects in the German sample.
Technique	genotyping
Statistical Method	X2 test
Result Summary	No evidence was found for association in the new samples when analysed individually; however, in the joint analysis of the two Scottish samples, a region B haplotype comprising two SNPs (rs6988339 and rs3757930) was associated with SCZ and the combined case group (SCZ: p=0.0037, OR=1.3, 95% CI: 1.1-1.6; BPD+SCZ: p=0.0080, OR=1.2, 95% CI: 1.1-1.5), with these associations withstanding multiple testing correction at the single-test level (SCZ: p(st)=0.022; BPD+SCZ: p(st)=0.044). This study supports the involvement of NRG1 variants in the less well studied 3' region in conferring susceptibility to SCZ and BPD in the Scottish population.