Details

Autor(en) / Beteiligte

• 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

Titel

Support for involvement of neuregulin 1 in schizophrenia pathophysiology

Ist Teil von

• Molecular psychiatry, 2005-04, Vol.10 (4), p.366-374

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2005

Link zum Volltext

Quelle

PBSC : Psychology and Behavioral Sciences Collection - Journals

Beschreibungen/Notizen

• 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.