Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, Munich, Germany.
J Psychiatr Res. 2012 Aug;46(8):973-9. doi: 10.1016/j.jpsychires.2012.04.017. Epub 2012 May 29.
Recent genome-wide association studies (GWAS) and metaanalyses revealed genetic associations for ANK3 (ankyrin 3) and CACNA1C (alpha 1C subunit of the L-type voltage gated calcium channel) with bipolar disorder (BPD). Several findings from clinical, epidemiological, and genetic studies point towards a common biological background of BPD and major depressive disorder (MDD). We were interested whether this also applies for ANK3 and CACNA1C and tested associations of single nucleotide polymorphisms (SNPs) in these genes with MDD in two Caucasian case-control samples. Sample 1 (Munich Antidepressant Response Signature Project/MARS - MDD) consisted of 720 depressed inpatients and 542 psychiatric healthy controls. Sample 2 (unipolar recurrent depression (URD)) consisted of 827 patients with URD and 860 psychiatric healthy controls. After stringent quality control we analyzed 262 SNPs (sample 1) and 504 SNPs (sample 2) and imputed further 5771 SNPs (sample 1) and 5534 SNPs (sample 2) from Hapmap Phase 2 data in the ANK3 and CACNA1C gene regions. Additionally, a metaanalysis of both samples was performed. Several SNPs in both genes were nominally associated with MDD with the highest association in the 3'-region of ANK3 (rs10994143, nominal p = 3.3*10(-4)) in the metaanalysis of both samples. None of these results remained significant after correction for multiple testing. No association of MDD with SNPs previously reported in BPD studies could be detected. By analyzing the LD-structure, our highest associated SNPs could not be linked to the SNPs previously reported in BPD. Regarding ANK3 and CACNA1C, our findings do not support a strong genetic link between BPD and MDD for these two genes.
最近的全基因组关联研究（GWAS）和荟萃分析揭示了 ANK3（锚蛋白 3）和 CACNA1C（L 型电压门控钙通道的 α1C 亚基）与双相障碍（BPD）的遗传关联。来自临床、流行病学和遗传学研究的一些发现指向 BPD 和重度抑郁症（MDD）的共同生物学基础。我们想知道这是否也适用于 ANK3 和 CACNA1C，并在两个高加索病例对照样本中测试了这些基因中单核苷酸多态性（SNP）与 MDD 的关联。样本 1（慕尼黑抗抑郁反应特征项目/MARS-MDD）包括 720 名住院抑郁症患者和 542 名精神健康对照组。样本 2（单相复发性抑郁症（URD））包括 827 名 URD 患者和 860 名精神健康对照组。经过严格的质量控制，我们分析了 ANK3 和 CACNA1C 基因区域中的 262 个 SNP（样本 1）和 504 个 SNP（样本 2），并从 Hapmap 第二阶段数据中进一步推断了 5771 个 SNP（样本 1）和 5534 个 SNP（样本 2）。此外，对两个样本进行了荟萃分析。两个基因中的几个 SNP 与 MDD 呈名义相关，ANK3 的 3'-区域的 SNP（rs10994143，名义 p=3.3*10(-4)）在两个样本的荟萃分析中相关性最高。在多重检验校正后，这些结果均无显著意义。未检测到与以前在 BPD 研究中报道的 SNP 相关的 MDD 关联。通过分析 LD 结构，我们发现与以前在 BPD 中报道的 SNP 相关的最高关联 SNP 无法与之相关联。关于 ANK3 和 CACNA1C，我们的研究结果不支持这两个基因在 BPD 和 MDD 之间存在强烈的遗传联系。
