Neuregulin 3 genetic variations and susceptibility to schizophrenia in a Chinese population.
BACKGROUND
The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population.


METHODS
Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis.


RESULTS
In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p < .05) with rs677221-C being the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95% confidence interval = 1.115-1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value = .0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p = .003 and p = .004, respectively). In the haplotype-transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p = .006) and over-transmission for haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were observed.


CONCLUSIONS
The result supports that the NRG3 gene is a susceptibility gene for schizophrenia.
Wang
Ying-Chieh
YC
Department of Psychiatry, Yuli Veterans Hospital, Hualien City, Taiwan, ROC.
Chen
Jen-Yeu
JY
Chen
Mao-Liang
ML
Chen
Chia-Hsiang
CH
Lai
I-Ching
IC
Chen
Tzu-Ting
TT
Hong
Chen-Jee
CJ
Tsai
Shih-Jen
SJ
Liou
Ying-Jay
YJ
D000328:Adult; D044466:Asian People / Q000235:genetics; D016009:Chi-Square Distribution; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020880:Neuregulins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D013624:Taiwan
D047908:Intracellular Signaling Peptides and Proteins; C486357:NRG3 protein, human; D020880:Neuregulins