A systematic review of genome-wide association studies of antipsychotic response

Josiah D. Allen; Jeffrey R Bishop

doi:10.2217/pgs-2018-0163

A systematic review of genome-wide association studies of antipsychotic response

Josiah D. Allen, Jeffrey R Bishop

Experimental and Clinical Pharmacology

Research output: Contribution to journal › Review article › peer-review

16 Scopus citations

Abstract

Clinical symptom response to antipsychotic medications is highly variable. Genome-wide association studies (GWAS) provide a 'hypothesis-free' method of interrogating the genome for biomarkers of antipsychotic response. We performed a systematic review of GWAS findings for antipsychotic efficacy or effectiveness. 14 studies met our inclusion criteria, ten of which examined antipsychotic response using quantitative rating scales to measure symptom improvement. 15 genome-wide significant loci were identified, seven of which were replicated in other antipsychotic GWAS publications: CNTNAP5, GRID2, GRM7, 8q24 (KCNK9), PCDH7, SLC1A1 and TNIK. Notably, four replicated loci are involved in glutamatergic pathways. Additional validation and evaluation of the biological significance of these markers is warranted. These markers should also be evaluated for clinical utility, especially in the context of other validated pharmacogenomic variants (e.g., CYP450 genes). These findings may generate new avenues for development of novel antipsychotic treatments.

Original language	English (US)
Pages (from-to)	291-306
Number of pages	16
Journal	Pharmacogenomics
Volume	20
Issue number	4
DOIs	https://doi.org/10.2217/pgs-2018-0163
State	Published - Mar 2019

Bibliographical note

Funding Information:
This work was in part supported by NIH grant MH083888 to JR Bishop. JR Bishop has no other financial conflicts to disclose. In the past 12 months, JD Allen has consulted for 23andMe, Clarigent Health, Prescient Medicine and Translational Software. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Publisher Copyright:
© 2019 Future Medicine Ltd.

Keywords

GWAS
antipsychotic
genome-wide association study
pharmacogenomics
psychopharmacology
schizophrenia
systematic review
treatment response

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural

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abstract = "Clinical symptom response to antipsychotic medications is highly variable. Genome-wide association studies (GWAS) provide a 'hypothesis-free' method of interrogating the genome for biomarkers of antipsychotic response. We performed a systematic review of GWAS findings for antipsychotic efficacy or effectiveness. 14 studies met our inclusion criteria, ten of which examined antipsychotic response using quantitative rating scales to measure symptom improvement. 15 genome-wide significant loci were identified, seven of which were replicated in other antipsychotic GWAS publications: CNTNAP5, GRID2, GRM7, 8q24 (KCNK9), PCDH7, SLC1A1 and TNIK. Notably, four replicated loci are involved in glutamatergic pathways. Additional validation and evaluation of the biological significance of these markers is warranted. These markers should also be evaluated for clinical utility, especially in the context of other validated pharmacogenomic variants (e.g., CYP450 genes). These findings may generate new avenues for development of novel antipsychotic treatments.",

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note = "Funding Information: This work was in part supported by NIH grant MH083888 to JR Bishop. JR Bishop has no other financial conflicts to disclose. In the past 12 months, JD Allen has consulted for 23andMe, Clarigent Health, Prescient Medicine and Translational Software. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: {\textcopyright} 2019 Future Medicine Ltd.",

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N2 - Clinical symptom response to antipsychotic medications is highly variable. Genome-wide association studies (GWAS) provide a 'hypothesis-free' method of interrogating the genome for biomarkers of antipsychotic response. We performed a systematic review of GWAS findings for antipsychotic efficacy or effectiveness. 14 studies met our inclusion criteria, ten of which examined antipsychotic response using quantitative rating scales to measure symptom improvement. 15 genome-wide significant loci were identified, seven of which were replicated in other antipsychotic GWAS publications: CNTNAP5, GRID2, GRM7, 8q24 (KCNK9), PCDH7, SLC1A1 and TNIK. Notably, four replicated loci are involved in glutamatergic pathways. Additional validation and evaluation of the biological significance of these markers is warranted. These markers should also be evaluated for clinical utility, especially in the context of other validated pharmacogenomic variants (e.g., CYP450 genes). These findings may generate new avenues for development of novel antipsychotic treatments.

AB - Clinical symptom response to antipsychotic medications is highly variable. Genome-wide association studies (GWAS) provide a 'hypothesis-free' method of interrogating the genome for biomarkers of antipsychotic response. We performed a systematic review of GWAS findings for antipsychotic efficacy or effectiveness. 14 studies met our inclusion criteria, ten of which examined antipsychotic response using quantitative rating scales to measure symptom improvement. 15 genome-wide significant loci were identified, seven of which were replicated in other antipsychotic GWAS publications: CNTNAP5, GRID2, GRM7, 8q24 (KCNK9), PCDH7, SLC1A1 and TNIK. Notably, four replicated loci are involved in glutamatergic pathways. Additional validation and evaluation of the biological significance of these markers is warranted. These markers should also be evaluated for clinical utility, especially in the context of other validated pharmacogenomic variants (e.g., CYP450 genes). These findings may generate new avenues for development of novel antipsychotic treatments.

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A systematic review of genome-wide association studies of antipsychotic response

Abstract

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Keywords

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