Roby Yang
Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Psychiatr Genet. 2017 Dec;27(6):225-235. doi: 10.1097/YPG.0000000000000186.
Converging evidence has suggested ankyrin 3 (ANK3) as a risk gene for bipolar disorder (BD). However, association studies investigating its genetic variants and BD susceptibility have reported inconsistent results. In the present meta-analysis, we aimed to establish whether ANK3 single nucleotide polymorphisms (SNPs) confer increased risk for BD.
PubMed, Medline, PsycINFO, Embase, and Scopus were searched for literature published up to January 2017. Fourteen case-control studies met our eligibility criteria. We targeted ANK3 SNPs that have been reported by three or more studies to be included in the current meta-analysis, resulting in a final list of four SNPs: rs10994336, rs9804190, rs10994397, and rs1938526. Odds ratios (ORs) for the allele model were calculated using a random effect model as a measure of association. Additional experimental characteristics and between-study heterogeneity were explored using sensitivity test, subgroup analysis, and meta-regression techniques. Publication bias was also assessed using Egger's test and rank correlation test.
Overall, a significant association was found between BD and rs10994336 (OR=1.18; 95% confidence interval: 1.06-1.31; P=0.0027) as well as rs1938526 (OR=1.16; 95% confidence interval: 1.06-1.28; P=0.0016). Subsequent sensitivity analysis and publication bias test reaffirmed the stability and consistency of these results.
The current meta-analysis provides corroborating evidence suggesting two ANK3 SNPs are associated with an increased susceptibility for developing BD. However, broader coverage is needed on less explored SNPs to further elucidate the genetic effect of other ANK3 variants that may harbor potential BD risk.
越来越多的证据表明锚蛋白3（ANK3）是双相情感障碍（BD）的一个风险基因。然而，调查其基因变异与BD易感性的关联研究报告的结果并不一致。在本荟萃分析中，我们旨在确定ANK3单核苷酸多态性（SNP）是否会增加患BD的风险。
检索了截至2017年1月发表在PubMed、Medline、PsycINFO、Embase和Scopus上的文献。14项病例对照研究符合我们的纳入标准。我们将三项或更多研究报告的ANK3 SNP作为目标纳入当前的荟萃分析，最终得到四个SNP的列表：rs10994336、rs9804190、rs10994397和rs1938526。使用随机效应模型计算等位基因模型的优势比（OR），作为关联的一种度量。使用敏感性检验、亚组分析和荟萃回归技术探索了其他实验特征和研究间的异质性。还使用Egger检验和秩相关检验评估了发表偏倚。
总体而言，发现BD与rs10994336（OR=1.18；95%置信区间：1.06-1.31；P=0.0027）以及rs1938526（OR=1.16；95%置信区间：1.06-1.28；P=0.0016）之间存在显著关联。随后的敏感性分析和发表偏倚检验再次证实了这些结果的稳定性和一致性。
当前的荟萃分析提供了确凿的证据，表明两个ANK3 SNP与患BD的易感性增加有关。然而需要对较少研究的SNP进行更广泛的覆盖，以进一步阐明其他可能具有潜在BD风险的ANK3变异的遗传效应。
