Association of the 3' region of the neuregulin 1 gene with bipolar I disorder in the Chinese Han population.
BACKGROUND
Based on the function of neuregulin 1 (NRG1) in neurodevelopment, susceptibility to bipolar disorder presumably involves this gene. The 3' region of NRG1 contains the majority of the coding exons, and transcripts from this region encode 8 of the 9 known NRG1 isoforms; therefore, this region is likely to be predominant versus the 5' region in terms of their relative contributions to NRG1 function. We investigated the association between the 3' region of the NRG1 gene and bipolar I disorder (BPI) in the Chinese Han population and performed further analyses depending on the presence or absence of psychotic features.


METHODS
A total of 385 BPI patients and 475 healthy controls were recruited for this study. Thirty tag single nucleotide polymorphisms (SNPs) across the 3' region of the NRG1 gene were genotyped for allelic and haplotypic associations with BPI and subgroups with psychotic features (BPI-P) or without psychotic features (BPI-NP).


RESULTS
Individual marker analysis showed that 2 SNPs (rs12547858 and rs6468121) in this region were significantly associated with BPI. Moreover, subgroup analyses showed significant but marginal associations of rs6468121 with BPI-P and rs3757933 with BPI-NP. Haplotype analyses showed that 6 haplotypes were associated with BPI only.


CONCLUSIONS
The sample size was relatively small. The investigated tag SNPs only represented 83% of the information on the targeted region. There might be a retrospective bias in the subgroup analyses.


CONCLUSIONS
The results suggest that the 3' region of the NRG1 gene plays a role in BPI susceptibility in the Chinese Han population. In addition, the preliminary results show that BPI with psychotic features and BPI without psychotic features may constitute different sub-phenotypes; however, this finding should be confirmed in a larger population sample.
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China. Electronic address: coolliping@hotmail.com.
Liping
L
Cao
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Wenhao
W
Deng
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Lijie
L
Guan
Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Zhenxing
Z
Yang
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China; Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Yin
Y
Lin
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China; Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Xiaohong
X
Ma
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Xuan
X
Li
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Yuping
Y
Liu
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Biyu
B
Ye
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Guohui
G
Lao
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Yuwei
Y
Chen
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Huiwei
H
Liang
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Yuanfei
Y
Wu
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Yufen
Y
Ou
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Weijie
W
Huang
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China.
Wentao
W
Liu
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China; Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Qiang
Q
Wang
Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Brain Hospital, Guangzhou, Guangdong, PR China; Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Yingcheng
Y
Wang
Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Liansheng
L
Zhao
Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Tao
T
Li
Psychiatric Laboratory and Mental Health Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: hxxhu99@163.com.
Xun
X
Hu
D024509:3' Flanking Region / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D055815:Young Adult
D005819:Genetic Markers; D020890:Neuregulin-1
Bipolar disorder; Neuregulin 1 gene; Psychotic features