title: Support for NRG1 as a susceptibility factor for schizophrenia in a northern Swedish isolated population.
abstract: BACKGROUND
  Neuregulin 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.
  
  
  OBJECTIVE
  To determine the contribution of NRG1 to susceptibility for schizophrenia in a northern Swedish isolated population.
  
  
  METHODS
  Detailed 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.
  
  
  METHODS
  Outpatient and inpatient hospitals.
  
  
  METHODS
  A total of 486 unrelated patients with schizophrenia and 514 unrelated control individuals recruited from a northern Swedish isolated population.
  
  
  METHODS
  Association between markers and disease.
  
  
  RESULTS
  Analysis 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 </= P </= .04). Also, 2-, 3-, and 4-SNP windows that comprise these SNPs were associated (P < 3 x 10(-4)). One protective haplotype (0% vs 1.8%; P <5 x 10(-5)) and 1 disease risk-causing haplotype (40.4% vs 34.9%, P = .02) were defined.
  
  
  CONCLUSIONS
  The NRG1 gene contributes to the susceptibility for schizophrenia in the northern Swedish population.
authors: Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology, University of Antwerp, B-2610 Antwerp, Belgium.
authors: Maaike
authors: M
authors: Alaerts
authors: Shana
authors: S
authors: Ceulemans
authors: Diego
authors: D
authors: Forero
authors: Lotte N
authors: LN
authors: Moens
authors: Sonia
authors: S
authors: De Zutter
authors: Lien
authors: L
authors: Heyrman
authors: An-Sofie
authors: AS
authors: Lenaerts
authors: Karl-Fredrik
authors: KF
authors: Norrback
authors: Peter
authors: P
authors: De Rijk
authors: Lars-Göran
authors: LG
authors: Nilsson
authors: Dirk
authors: D
authors: Goossens
authors: Rolf
authors: R
authors: Adolfsson
authors: Jurgen
authors: J
authors: Del-Favero
mesh_terms: D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers; D020890:Neuregulin-1