ANK3 and CACNA1C-Missing genetic link for bipolar disorder and major depressive disorder in two German case-control samples
ANK3 and CACNA1C-Missing genetic link for bipolar disorder and major depressive disorder in two German case-control samples
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DOI：
10.1016/j.jpsychires.2012.04.017
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发表时间：
2012-08-01
影响因子：
4.8
通讯作者：
Lucae, Susanne
中科院分区：
文献类型：
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作者：
Kloiber, Stefan;Czamara, Darina;Lucae, Susanne
最近的全基因组关联研究（GWAS）和荟萃分析显示ANK3（锚蛋白3）和CACNA1C （l型电压门控钙通道α 1C亚基）与双相情感障碍（BPD）存在遗传关联。来自临床、流行病学和遗传学研究的一些发现指出了BPD和重度抑郁症（MDD）的共同生物学背景。我们对ANK3和CACNA1C是否也适用于此感兴趣，并在两个高加索病例对照样本中测试了这些基因的单核苷酸多态性（snp）与MOD的关联。样本1（慕尼黑抗抑郁反应签名项目/MARS - MOD）由720名住院抑郁症患者和542名精神健康对照者组成。样本2（单极复发性抑郁症（URD））由827名单极复发性抑郁症患者和860名精神健康对照者组成。经过严格的质量控制，我们分析了262个snp（样本1）和504个snp（样本2），并从ANK3和CACNA1C基因区域的Hapmap Phase 2数据中进一步输入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名义上与MDD相关，在两个样本的荟萃分析中，ANK3的3'-区域的相关性最高（rs10994143，名义p = 3.3*10(-4)）。经过多次检验校正后，这些结果都不显著。在BPD研究中未发现MDD与snp的关联。通过分析ld结构，我们的最高相关snp不能与先前报道的BPD中的snp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MOD之间有很强的遗传联系。(C) 2012 Elsevier Ltd.版权所有。
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 MOD in two Caucasian case-control samples. Sample 1 (Munich Antidepressant Response Signature Project/MARS - MOD) 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 meta-analysis 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 MOD for these two genes. (C) 2012 Elsevier Ltd. All rights reserved.