Dataset Information

GADL1 variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

ABSTRACT: Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders.To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (GADL1) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder.Frequencies of manic and depressive episodes between carriers and non-carriers of the effective GADL1 rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (n=215).GADL1 rs17026688 T carriers had significantly lower frequencies of recurrent affective episodes than non-T carriers during the cumulative period of good adherence, but not during those of poor adherence.GADL1 rs17026688 and medication adherence jointly predict response to lithium maintenance treatment in Han Chinese BPI patients.None.© The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

SUBMITTER: Chen CK

PROVIDER: S-EPMC5015003 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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<i>GADL1</i> variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

Chen Chih-Ken CK Lee Chau-Shoun CS Chen Hsuan-Yu HY Wu Lawrence Shih-Hsin LS Chang Jung-Chen JC Liu Chia-Yih CY Cheng Andrew Tai-Ann AT

BJPsych open 20160908 5

<h4>Background</h4>Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders.<h4>Aims</h4>To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (<i>GADL1</i>) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder.<h4>Method</h4>Frequencies of manic and depressive episodes between carriers and non-carriers o ...[more]

PMID: 27703793

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Project description:BACKGROUND:Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS:Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS:A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37?×?10(-8); rs78015114, p=1·31?×?10(-8); rs74795342, p=3·31?×?10(-9); and rs75222709, p=3·50?×?10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION:The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING:Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

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GADL1 variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

Publications

<i>GADL1</i> variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

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