• Maaike Alaerts, Shana Ceulemans, Diego Forero, Lotte N Moens, Sonia De Zutter, Lien Heyrman, An-Sofie Lenaerts, Karl-Fredrik Norrback, Peter De Rijk, Lars-Göran Nilsson, Dirk Goossens, Rolf Adolfsson, and Jurgen Del-Favero.
• Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology, University of Antwerp, B-2610 Antwerp, Belgium.
• Arch. Gen. Psychiatry. 2009 Aug 1; 66 (8): 828-37.

ContextNeuregulin 1 (NRG1), a growth factor involved in neurodevelopment, myelination, neurotransmitter receptor expression, and synaptic plasticity, first joined the list of candidate genes for schizophrenia when a 7-marker haplotype at the 5' end of the gene (Hap(ICE)) was shown to be associated with the disorder in the Icelandic population. Since then, more genetic and functional evidence has emerged, which supports a role for NRG1 in the development of schizophrenia.ObjectiveTo determine the contribution of NRG1 to susceptibility for schizophrenia in a northern Swedish isolated population.DesignDetailed linkage disequilibrium (LD)-based patient-control association study. This is the first study to type and analyze the 7 Hap(ICE) markers and a set of 32 HapMap tagging single-nucleotide polymorphisms (SNPs) that represents variants with a minor allele frequency of at least 1% and fully characterizes the LD structure of the 5' part of NRG1.SettingOutpatient and inpatient hospitals.ParticipantsA total of 486 unrelated patients with schizophrenia and 514 unrelated control individuals recruited from a northern Swedish isolated population.Main Outcome MeasuresAssociation between markers and disease.ResultsAnalysis of the Hap(ICE) markers showed the association of a 7-marker and 2-microsatellite haplotype, different from the haplotypes associated in the Icelandic population and overrepresented in northern Swedish control individuals. Subsequently, a more detailed analysis that included all 37 genotyped SNPs was performed by investigating haplotypic association, dependent and independent of LD block structure. We found significant association with 5 SNPs located in the second intron of NRG1 (.007 ConclusionThe NRG1 gene contributes to the susceptibility for schizophrenia in the northern Swedish population.

25 keywords...

hide…