Convergent analysis of genome ‐wide genotyping and transcriptomic data suggests association of zinc finger genes with lithium response in bipolar disorder

In this study, we applied an integrated analytical approach using genome ‐wide expression and genotyping data from BD patients to identify lithium‐responsive genes that may serve as biomarkers of its efficacy. To this purpose, we tested the effect of treatment with lithium chloride 1 mM on the transcriptome of lymphoblasts from 10 lithium responders (LR) and 10 nonre sponders (NR) patients and identified genes significantly influenced by the treatment exclusively in LR. These findings were integrated with gene‐based analysis on genome‐wide genotyping data from an extended sample of 205 BD patients characterized for lithium response. The expression of 29 gene s was significantly changed by lithium exclusively in LR. Gene‐based analysis showed that two of these genes, zinc finger protein 429 (ZNF429) and zinc finger protein 493 (ZNF493), were also significantly associated with lithium response. Validation with quantitative real‐time polymerase chain r eaction confirmed the lithium‐induced downregulation ofZNF493 in LR (p = .036). Using convergent analyses of genome‐wide expression and genotyping data, we identifiedZNF493 as a potential lithium ‐responsive target that may be involved in modulating lithium efficacy in BD. To our knowledge, this is the first evidence supporting the involvement of zinc finger proteins in lithium response.
Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics - Category: Genetics & Stem Cells Authors: Tags: RESEARCH ARTICLE Source Type: research