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Molecular psychiatry DOI:10.1038/

Support for involvement of neuregulin 1 in schizophrenia pathophysiology.

Publication TypeJournal Article
Year of Publication2005
AuthorsPetryshen, TL, Middleton, FA, Kirby, A, Aldinger, KA, Purcell, S, Tahl, AR, Morley, CP, McGann, L, Gentile, KL, Rockwell, GN, Medeiros, HM, Carvalho, C, Macedo, A, Dourado, A, Valente, J, Ferreira, CP, Patterson, NJ, Azevedo, MH, Daly, MJ, Pato, CN, Pato, MT, Sklar, P
JournalMolecular psychiatry
Pages366-74, 328
Date Published2005/04/01

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.