BACKGROUND: A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese. METHODS: We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients. RESULTS: The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06-1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects. LIMITATIONS: The relative small sample size in BD group should be considered a limitation of this study. CONCLUSIONS: Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.
BACKGROUND: A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese. METHODS: We genotyped three potentially functional polymorphisms in 635 MDDpatients, 286 BD patients and 730 normal, control patients. RESULTS: The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06-1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDDpatients and control subjects. LIMITATIONS: The relative small sample size in BD group should be considered a limitation of this study. CONCLUSIONS: Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.
Authors: Ming Li; Xiong-jian Luo; Mikael Landén; Sarah E Bergen; Christina M Hultman; Xiao Li; Wen Zhang; Yong-Gang Yao; Chen Zhang; Jiewei Liu; Manuel Mattheisen; Sven Cichon; Thomas W Mühleisen; Franziska A Degenhardt; Markus M Nöthen; Thomas G Schulze; Maria Grigoroiu-Serbanescu; Hao Li; Chris K Fuller; Chunhui Chen; Qi Dong; Chuansheng Chen; Stéphane Jamain; Marion Leboyer; Frank Bellivier; Bruno Etain; Jean-Pierre Kahn; Chantal Henry; Martin Preisig; Zoltán Kutalik; Enrique Castelao; Adam Wright; Philip B Mitchell; Janice M Fullerton; Peter R Schofield; Grant W Montgomery; Sarah E Medland; Scott D Gordon; Nicholas G Martin; Marcella Rietschel; Chunyu Liu; Joel E Kleinman; Thomas M Hyde; Daniel R Weinberger; Bing Su Journal: Br J Psychiatry Date: 2015-09-03 Impact factor: 9.319
Authors: B Etain; M Lajnef; A Henrion; A A Dargél; L Stertz; F Kapczinski; F Mathieu; C Henry; S Gard; J P Kahn; M Leboyer; S Jamain; F Bellivier Journal: Sci Rep Date: 2015-11-06 Impact factor: 4.379