Linkage and association of schizophrenia with genetic variations in the locus of neuregulin 1 in Korean population.
Chromosome 8p21-12 has been reported to be a susceptibility locus for schizophrenia based on genome-wide linkage scans. After neuregulin 1 (NRG1) was identified as a positional candidate gene for schizophrenia in this locus, several independent association studies have reported controversial results. To determine whether genetic variations in this locus are associated with schizophrenia in the Korean population, we investigated multiplex families and unrelated patients using linkage and association analyses. Seven microsatellite markers in 8p21-12 were genotyped for 40 families with schizophrenia, and a non-parametric linkage analysis was applied. The association study was performed with 242 unrelated schizophrenia patients and the same number of normal controls for three single nucleotide polymorphisms (SNPs), two microsatellite markers and their haplotypes. A significant linkage signal was observed on D8S1769, which is located 352 kb upstream of the 5' end of the first exon of NRG1 for two ("narrow" and "narrow with auditory hallucination (AH)") of the three adopted phenotype classes. In the association study, the G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with AHs. We also found haplotypes which were associated with schizophrenia with a protective effect. This study provides additional suggestive evidence for both the linkage and association of genetic variations on 8p12, a locus of NRG1, with schizophrenia. NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium (LD) with a causal locus of this illness.
Kim
Jong Won
JW
Department of Laboratory Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
Lee
Yu-Sang
YS
Cho
Eun-Young
EY
Jang
Yong Lee
YL
Park
Dong Yeon
DY
Choi
Kyeong-Sook
KS
Jeun
Hyun Ok
HO
Cho
Seung-Hee
SH
Jang
Sue-Yon
SY
Hong
Kyung Sue
KS
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1