Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder.
Schizophrenia (SCZ) and bipolar disorder (BPD) are severe heritable psychiatric disorders involving a complex genetic aetiology. Neuregulin 1 (NRG1) is a leading candidate gene for SCZ, and has recently been implicated in BPD. We previously reported association of two NRG1 haplotypes with SCZ and BPD in a Scottish case-control sample. One haplotype is located at the 5' end of the gene (region A), and the other is located at the 3' end (region B). Here, association to haplotypes within regions A and B was assessed in patients with SCZ and BPD in a second Scottish case-control sample and in the two Scottish samples combined. Association to region B was also assessed in patients with SCZ and BPD in a German case-control sample, and in all three samples combined. 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.
Walker
Rosie M
RM
Medical Genetics Section, Centre for Molecular Medicine and Institute of Genetics and Molecular Medicine, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK. R.M.Walker-2@sms.ed.ac.uk
Christoforou
Andrea
A
Thomson
Pippa A
PA
McGhee
Kevin A
KA
Maclean
Alan
A
Mühleisen
Thomas W
TW
Strohmaier
Jana
J
Nieratschker
Vanessa
V
Nöthen
Markus M
MM
Rietschel
Marcella
M
Cichon
Sven
S
Morris
Stewart W
SW
Jilani
Omer
O
Stclair
David
D
Blackwood
Douglas H
DH
Muir
Walter J
WJ
Porteous
David J
DJ
Evans
Kathryn L
KL
D024509:3' Flanking Region; D024506:5' Flanking Region; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005858:Germany; D006239:Haplotypes; D006801:Humans; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D012606:Scotland
D020890:Neuregulin-1