Variant <i>GADL1</i> and Response to Lithium Therapy in Bipolar I Disorder

Chen, Chien-Hsiun; Lee, Chau‐Shoun; Lee, Ming-Ta Michael; Ouyang, Wen‐Chen; Chen, Chiao-Chicy; Chong, Mian‐Yoon; Wu, Jer‐Yuarn; Tan, Happy Kuy‐Lok; Lee, Yi‐Ching; Chuo, Liang-Jen; Chiu, Nan‐Ying; Tsang, Hin-Yeung; Chang, T J; Lung, For‐Wey; Chiu, Chen-Huan; Chang, Cheng-Ho; Chen, Ying-Sheue; Hou, Yuh‐Ming; Chen, Cheng‐Chung; Lai, Te-Jen; Tung, Chun‐Liang; Chen, Chung-Ying; Lane, Hsien‐Yuan; Su, Tung‐Ping; Feng, Jung; Lin, Jin-Jia; Chang, Ching‐Jui; Teng, Po-Ren; Liu, Chia-Yih; Chen, Chih-Ken; Liu, I-Chao; Chen, Jiahn‐Jyh; Lu, Tung‐Wu; Fan, Chun-Chieh; Wu, Ching-Kuan; Li, Chang-Fang; Wang, Kathy Hsiao-Tsz; Wu, Lawrence Shih-Hsin; Peng, Hsin-Ling; Chang, Chun-Ping; Lu, Limin; Chen, Yuan-Tsong; Cheng, Andrew T. A.

doi:10.1056/nejmoa1212444

Cited by 137 publications

(96 citation statements)

References 27 publications

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“…Similarly, polygenic approaches that tried to elucidate the overall genome-wide genetic influences on antidepressant treatment response in MDD have failed to predict antidepressant efficacy in It is a highly polymorphic gene that encodes an enzyme in the CYPsuperfamily [121] Polymorphisms in the CYP2D6 gene may influence the metabolism and response of antidepressant response [16,67,90]. Similar to other CYP enzymes, CYP2D6 may result in a different ability to metabolize drugs (poor or ultrarapid)…”

Section: -Hydroxytryptamine Receptor 2amentioning

confidence: 99%

“…A GWAS by the International Consortium on Lithium Genetics (ConLi + Gen), incorporating over 2500 bipolar patients from Europe, USA, Asia, and Australia found a single locus of four linked SNPs on chromosome 21 [56]. Another GWAS by the Taiwan Bipolar Consortium involved 294 bipolar patients of Han Chinese descent and identified two SNPs in high linkage disequilibrium, located in the introns of GADL1 gene [16]. The third GWAS that involved 3874 patients with BPD using subjectively (self-reported) and objectively defined (clinically documented) lithium response data from Sweden and the UK revealed a SNP within the PLET1 gene associated with lithium-responsive patients in BPD [].…”

Section: Lithium Treatment For Bipolar Disordermentioning

confidence: 99%

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Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry. So far, the progress of uncovering single nucleotide polymorphisms (SNPs) underpinning treatment efficacy in mood disorders (e.g., SNPs associated with selective serotonin re-uptake inhibitors or lithium treatment response in patients with bipolar disorder and major depressive disorder) are encouraging, but not adequate. Genetic studies have pointed to a number of SNPs located at candidate genes that possibly influence response to; (a) antidepressants COMT, HTR2A, HTR1A, CNR1, SLC6A4, NPY, MAOA, IL1B, GRIK4, BDNF, GNB3, FKBP5, CYP2D6, CYP2C19, and ABCB1 and (b) mood stabilizers (lithium) 5-HTT, TPH, DRD1, FYN, INPP1, CREB1, BDNF, GSK3β, ARNTL, TIM, DPB, NR3C1, BCR, XBP1, and CACNG2. We suggest three alternative and complementary strategies to implement knowledge gained from pharmacogenomic studies. The first strategy can be to implement diagnostic, therapeutic, or prognostic genetic testing based on candidate genes or gene products. The second alternative is an integrative analysis (systems genomics approach) to combine omics data obtained from the different pillars of omics investigation, including genomics, epigenomes, proteomics, metabolomics and microbiomes. The main goal of system genomics is an identification and understanding of biological pathways, networks, and modules underlying drug-response. The third strategy aims to the development of multivariable diagnostic or prognostic algorithms (tools) combining individual's genomic information (polygenic score) with other predictors (e.g., omics pillars, neuroimaging, and clinical characteristics) to finally predict therapeutic outcomes. An integration of molecular science with that of traditional clinical practice is the way forward to drug discoveries and novel therapeutic approaches and to characterize psychiatric disorders leading to a better predictive, preventive, and personalized medicine (PPPM) in psychiatry. With future advances in the omics technology and methodological developments for data integration, the goal of PPPM in psychiatry is promising.

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Section: -Hydroxytryptamine Receptor 2amentioning

confidence: 99%

Section: Lithium Treatment For Bipolar Disordermentioning

confidence: 99%

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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“…The second GWAS in this list is from a Taiwanese group; they reported genome-wide significance for a SNP in the glutamate decarboxylase-like protein 1 gene (GADL1) that is only present in Asians. However, this finding could not be replicated in other independent samples from Asia (14). Finally, the largest GWAS of lithium response so far is the study of the Consortium on Lithium Genetics (ConLiGen; www.ConLiGen.org).…”

Section: Dusunen Adam the Journal Of Psychiatry And Neurological Sciementioning

confidence: 91%

Update on Research into the Genetics and Pharmacogenetics of Bipolar Disorder

Schulze¹,

Özkan²

2017

Dusunen Adam

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“…More recently, GWAS methods have been applied to look for common risk variants, but the reported studies have been relatively small. Where promising findings have been reported (an example being a genetic variation at the GADL1 gene proposed as a sensitive (93 %) predictor of lithium response in a Han Chinese population) [50], these have generally failed to replicate in subsequent studies [51][52][53][54]. This area remains one of substantial interest as there is evidence of a genetic contribution to the variability in treatment response of current treatments including clozapine [55] and lithium [56].…”

Section: Treatment Responsementioning

confidence: 99%

Biomarkers for Psychosis: the Molecular Genetics of Psychosis

Corvin

Harold

2015

Curr Behav Neurosci Rep

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Substantial progress has been made in understanding the genetic architecture of psychosis but also in identifying a subset of the contributory risk genes. At a molecular level, there is significant overlap between major psychotic disorders (e.g., schizophrenia, bipolar disorder, schizoaffective disorder) but also moderate levels of covariance with other psychiatric conditions (e.g., depression, autistic spectrum disorders). Despite advances, psychosis remains a clinical, syndromal diagnosis in almost all cases. The challenge is to translate progress in genomics into understanding of biological processes that can be objectively measured to inform risk, diagnosis, treatment response, and disease severity/outcome. With this in mind, we review recent results and ongoing research in psychosis genomics.

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Variant GADL1 and Response to Lithium Therapy in Bipolar I Disorder

Abstract: Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).

Cited by 137 publications

References 27 publications

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

Update on Research into the Genetics and Pharmacogenetics of Bipolar Disorder

Biomarkers for Psychosis: the Molecular Genetics of Psychosis

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