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- Title
Support for involvement of neuregulin 1 in schizophrenia pathophysiology.
- Authors
Petryshen, T L; Middleton, F A; Kirby, A; Aldinger, K A; Purcell, S; Tahl, A R; Morley, C P; McGann, L; Gentile, K L; Rockwell, G N; Medeiros, H M; Carvalho, C; Macedo, A; Dourado, A; Valente, J; Ferreira, C P; Patterson, N J; Azevedo, M H; Daly, M J; Pato, C N; Pato, M T; Sklar, P
- Abstract
Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ("Hap(ICE)"), and two haplotypes located in the 3' end of NRG1 (all P<0.05). However, association was not detected with Hap(ICE) itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (P=0.039). Significant positive correlations (P<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia.
- Publication
Molecular psychiatry, 2005, Vol 10, Issue 4, p366
- ISSN
1359-4184
- Publication type
Journal Article
- DOI
10.1038/sj.mp.4001608