Association of a haplotype in the NRG1 gene with schizophrenia: a case-control study

Abstract Objectives Schizophrenia (SZ) is a severe multifactorial disease. NRG1 is a gene acting in the development of SZ. A number of NRG1 single nucleotide polymorphisms (SNPs) and their haplotypes are associated with SZ. In the present study, we investigated the association of a NRG1 haplotype (G-C in rs6988339-rs3757930 frame) which was reported to be associated with SZ, and two other SNPs in the same gene (rs74942016, rs80127039) whose rare missense alleles were found in SZ patients. Also, we analyzed disease associations of potential new haplotypes constructed by the variants of these SNPs. Methods We genotyped 4 SNPs in a sample consisting of 302 SZ patients and 333 controls from a local Turkish population. We tested the disease associations of these variants at single SNP, haplotype and diplotype levels in case-control design. Results At single SNP level, the CC genotype of rs3757930 was associated with SZ (p=0.038). The previously reported association of G-C haplotype in rs6988339-rs3757930 frame was absent (p=0.416), but we found another haplotype (C-G in rs3757930-rs74942016, p=0.018) and three diplotypes (A-C/G-C diplotype of rs6988339-rs3757930 frame, C-G/C-G diplotype of rs3757930-rs74942016 frame, and A-C-G/G-C-G diplotype of rs6988339-rs3757930-rs74942016 frame) associated with schizophrenia in our sample. Conclusions Our study indicated the associations of a SNP, a haplotype, and a diplotype of NRG1 with schizophrenia and supported the involvement of NRG1 gene in the development of the disease. Since our sample was collected from a limited geographic area, the associations we have reported need to be supported by further studies in different populations.