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.

Limitations: 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.

Conclusion: 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.