A Systematic Review of Genome-Wide Association Studies of Antipsychotic Response

Allen, Josiah D.; Bishop, Jeffrey R.

doi:10.2217/pgs-2018-0163

Cited by 33 publications

(19 citation statements)

References 81 publications

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“…To our knowledge, however, our study is the first where genetic polymorphism in these two genes has been associated with pain sensitivity measurements. On the other hand, the four other genes in the pathway, PTPRD, DLG2, GPC6, and GRID2, have been all associated with diverse neurological disorders [31][32][33][34]. This observation supports earlier findings that neurological disorders and pain sensitivity are intimately linked [35].…”

Section: Discussionsupporting

confidence: 81%

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Fontanillas

Kless

Bothmer

et al. 2019

Preprint

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Altered pain sensitivity is believed to play an important role in the development of chronic pain, a common debilitating condition affecting an estimated 1 of 5 adults. Pain sensitivity varies broadly between individuals, and it is notoriously difficult to measure in large population. Although pain sensitivity is known to be moderately heritable, only a limited numbers of genetics studies have been published, with limited success at identifying the genetic architecture of pain sensitivity. In this study, we deployed a pain sensitivity questionnaire (PSQ) and an at-home version of cold pressor test (CPT) in a large genotyped cohort. We performed genome-wide association study (GWAS) analysis on the PSQ scores and CPT duration, collected for 25,321 and 6,853 participants, respectively. Despite a reasonably large sample size, we identified only one genome-wide significant locus, located in the TSSC1 gene, associated with PSQ score. Genetic correlation analysis suggested that PSQ has several traits that are correlated with chronic pain states and lifestyle factors. We found that PSQ score are positively correlated to neck and shoulder pain that lasts more than 3 months and negatively correlated to acute pain sensations like fracture. Gene-based analysis followed by pathway analysis suggested that GWAS results are enriched in genes controlling Thyroid peroxidase and Melanin production. We showed that genetic variation in MC1R gene and redhead hair pigmentation is associated with an increase of pain sensitivity measured by the PSQ scores.

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Section: Discussionsupporting

confidence: 81%

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Fontanillas

Kless

Bothmer

et al. 2019

Preprint

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“…Some studies have also reported that SNP rs2228622 and rs7022369 in the SLC1A1 gene were susceptibility gene sites for SZ ( 15 , 19 ). Moreover, the SNP rs16921385, located in an intron of SLC1A1 , was found to be associated with risperidone treatment response ( 22 , 30 ). Therefore, SLC1A1 variation was associated with the pathogeny of SZ.…”

Section: Discussionmentioning

confidence: 99%

Solute Carrier Family 1 (SLC1A1) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population

Chen

et al. 2020

Front. Psychiatry

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Objective Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene ( SLC1A1 ) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results Significant associations were found in genotype and allele frequencies for SNPs rs10815017 ( p = 0.002, 0.030, respectively) and rs2026828 ( p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 ( p = 0.020) and rs7024664 ( p = 0.021) and allele frequency at rs3780412 ( p = 0.026) and rs10974573 ( p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 ( p = 0.015), rs2026828 ( p = 0.011), and rs3780411 ( p = 0.040) in males, and rs7021569 in females ( p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 ( p = 0.003), and rs7021569 ( p = 0.045) in males, and rs10974619 in females ( p = 0.044). However, those associations disappeared after Bonferroni’s correction ( p ’s > 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls ( χ 2 = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ ( p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms.

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“…To this end, Allen and Bishop performed a systematic review of the existing literature for GWAS findings for antipsychotic treatment response. In this review, 15 genome-wide significant loci were identified (CNTNAP5, GRID2, GRM7, 8q24 (KCNK9), PCDH7, SLC1A1 and TNIK), seven of which were replicated in other antipsychotic genome-wide studies [10]. However, further validation of these findings is needed in order to demonstrate the clinical utility of these pharmacogenomics markers.…”

Section: Introductionmentioning

confidence: 97%

Delineating significant genome-wide associations of variants with antipsychotic and antidepressant treatment response: implications for clinical pharmacogenomics

Koromina¹,

Koutsilieri²,

Patrinos³

2020

Hum Genomics

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Background: Genome-wide association studies (GWAS) have significantly contributed to the association of many clinical conditions and phenotypic characteristics with genomic variants. The majority of these genomic findings have been deposited to the GWAS catalog. So far, findings uncovering associations of single nucleotide polymorphisms (SNPs) with treatment efficacy in mood disorders are encouraging, but not adequate. Methods: Statistical, genomic, and literature information was retrieved from EBI's GWAS catalog, while we also searched for potential clinical information/clinical guidelines in well-established pharmacogenomics databases regarding the assessed drug-SNP correlations of the present study. Results: Here, we provide an overview of significant genome-wide associations of SNPs with the response to commonly prescribed antipsychotics and antidepressants. Up to date, this is the first study providing novel insight in previously reported pharmacogenomics associations for antipsychotic/antidepressant treatment. We also show that although there are published CPIC guidelines for antidepressant agents, as well as the FDA labels include genome-based drug prescription information for both antipsychotic and antidepressant treatments, there are no specific clinical guidelines for the assessed drug-SNP correlations of this study. Conclusions: Our present findings suggest that more effort should be implemented towards identifying GWAsignificant antipsychotic and antidepressant pharmacogenomics correlations. Moreover, additional functional studies are required in order to characterise the potential role of the assessed SNPs as biomarkers for the response of patients to antipsychotic/antidepressant treatment.

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A Systematic Review of Genome-Wide Association Studies of Antipsychotic Response

Cited by 33 publications

References 81 publications

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test

Solute Carrier Family 1 (SLC1A1) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population

Delineating significant genome-wide associations of variants with antipsychotic and antidepressant treatment response: implications for clinical pharmacogenomics

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