Association study of GRM7 polymorphisms with major depressive disorder in the Chinese Han population

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Major depressive disorder (MDD) is a polygenic and worldwide psychiatric disease. It is characterized by low mood, an inability to concentrate, and lack of interest (Lee et al., 2012). The disability, high recurrence, and severe neurological damage caused by MDD result in heavy burdens for individuals, families, and society. Moreover, it is the major cause of suicides. For the past few years, Shyn et al. (2009) and Hamilton (2011) have reported that the metabotropic glutamate receptor 7 (GRM7) gene was associated with MDD, respectively. However, other studies have shown inconsistent results (Verbeek et al., 2013). Given the differences in the results of previous studies, we designed a case–control study to test the association between GRM7 single nucleotide polymorphisms (SNPs) and MDD in Chinese Han origin.
For the case–control study, we recruited 1414 unrelated individuals, including 568 MDD patients (308 women and 260 men, age: 35.97±12.90 years) and 846 healthy controls (361 women and 485 men, age: 33.93±10.25 years). Clinical interviews were carried out by two independent psychiatrists. Psychiatric diagnoses were established using Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria assessed with the Structured Clinical Interview for DSM Axis I and the 17-item Hamilton Depression Rating Scale was administered to assess the severity of the depressive episode. All of the control participants were subjected to an interview to exclude psychiatric disorders with Mini-International Neuropsychiatric Interview (version 5.0.0) and had no history of psychiatric illness. Mini-International Neuropsychiatric Interview was also administered to exclude psychiatric comorbidity. DNA of all the participants were acquired through the standard phenol–chloroform method from peripheral blood samples. We used SHEsis (http://analysis.bio-x.cn/myAnalysis.php) to analyze Hardy–Weinberg equilibrium, allelic distributions, genotypic distributions, and pairwise linkage disequilibrium (Shi and He, 2005).
Four single nucleotide polymorphisms (rs9814881, rs13353402, rs9870680, and rs1531939) were genotyped successfully using a matrix-assisted laser desorption/ionization time of flight mass spectrometer on a MassARRAY Analyzer 4 platform (Sequenom, San Diego, California, USA). All the single nucleotide polymorphisms were in Hardy–Weinberg equilibrium among patients and healthy controls. Genotypes of cases versus controls were distributed as follows: rs9814881 AA 430 : 676, AG 108 : 161 GG 12 : 5, rs13353402 AA 0 : 1, AG 22 : 46, GG 536 : 798, rs9870680 CC 49 : 74, CT 225 : 338, TT 287 : 431, and rs1531939 CC 19 : 38, CG 181 : 243, GG 345 : 561. We identified SNP rs9814881 in GRM7 with a significant genotype association with MDD (P=0.0287). For the allele frequencies, however, there were no significant discrepancies between healthy controls and patients with major depressive disorder. D′ and r2 were calculated for all random combinations of the four SNPs (data was not shown). The results showed that there was no strong linkage disequilibrium among rs9814881, rs13353402, rs9870680, and rs1531939. Furthermore, haplotype analyses were carried out for the four SNPs. No significant association was found among rs9814881, rs13353402, rs9870680, and rs1531939. The power was more than 80% when genotype relative risk was set at 1.3–1.5 under a multiplicative model of inheritance.
In conclusion, the results of this study indicate that the GRM7 rs9814881 might be associated with MDD in the Chinese Han population. To validate our results, further studies with larger numbers of samples and more SNPs coverage for genotyping are needed. MDD is a severe and complex mental disorder that is influenced by genetic, psychological, and environmental factors. Therefore, it is necessary and useful to carry out a comprehensive analysis of genetic role of GRM7 in MDD.
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