Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.