Genotype-based ancestral background consistently predicts efficacy and side effects across treatments in CATIE and STARD

Only a subset of patients will typically respond to any given prescribed drug. The time it takes clinicians to declare a treatment ineffective leaves the patient in an impaired state and at unnecessary risk for adverse drug effects. Thus, diagnostic tests robustly predicting the most effective and s...

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Bibliographic Details
Published in:PloS one 2013-02, Vol.8 (2), p.e55239
Main Authors: Adkins, Daniel E, Souza, Renan P, Aberg, Karolina, Clark, Shaunna L, McClay, Joseph L, Sullivan, Patrick F, van den Oord, Edwin J C G
Format: Article
Language:English
Subjects:
Algorithms
Analysis
Antipsychotics
Biology
Biomarkers
Clinical trials
Complications and side effects
Diagnostic systems
Drug development
Drug efficacy
Drug therapy
Drugs
Epidemiology
Genetic aspects
Genetic markers
Genetic Markers - genetics
Genetic Testing - methods
Genetics
Genome, Human
Genome-Wide Association Study
Genomes
Genomics
Genotype
Humans
Mathematics
Medical research
Medicin och hälsovetenskap
Medicine
Mental depression
Null hypothesis
Patients
Pharmacology
Pharmacy
Polymorphism, Single Nucleotide
Precision medicine
Precision Medicine - methods
Prescription Drugs - adverse effects
Prescription Drugs - therapeutic use
Prescriptions (Drugs)
Principal components analysis
Psychiatry
Psychosis
Psychotropic drugs
Quality control
Race
Regression analysis
Schizophrenia
Self Report
Side effects
Single-nucleotide polymorphism
Statistical analysis
Statistical methods
Statistical tests
Studies
Treatment Outcome
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Summary:Only a subset of patients will typically respond to any given prescribed drug. The time it takes clinicians to declare a treatment ineffective leaves the patient in an impaired state and at unnecessary risk for adverse drug effects. Thus, diagnostic tests robustly predicting the most effective and safe medication for each patient prior to starting pharmacotherapy would have tremendous clinical value. In this article, we evaluated the use of genetic markers to estimate ancestry as a predictive component of such diagnostic tests. We first estimated each patient's unique mosaic of ancestral backgrounds using genome-wide SNP data collected in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) (n = 765) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) (n = 1892). Next, we performed multiple regression analyses to estimate the predictive power of these ancestral dimensions. For 136/89 treatment-outcome combinations tested in CATIE/STAR*D, results indicated 1.67/1.84 times higher median test statistics than expected under the null hypothesis assuming no predictive power (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0055239