Automated Pharmacogenomic Reports for Clinical Genome Sequencing.

Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing that could help inform medication selection or dosing throughout the lifespan. Implementation of pharmacogenomic reporting must address several challenges, including inherent limitations in short-read genome sequencing methods, gene and variant selection, standardization of genotype and phenotype nomenclature, and choice of guidelines and drugs to report. An automated pipeline, lmPGX, was developed as an end-to-end solution that produces two versions of a pharmacogenomic report, presenting either Clinical Pharmacogenetics Implementation Consortium or US Food and Drug Administration guidelines for 12 genes.

Genome-wide association study of short-acting β2-agonists. A novel genome-wide significant locus on chromosome 2 near ASB3.

Rationale: β2-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable.

Objectives: To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma.

RNA-Seq transcriptome profiling identifies CRISPLD2 as a glucocorticoid responsive gene that modulates cytokine function in airway smooth muscle cells.

Asthma is a chronic inflammatory respiratory disease that affects over 300 million people worldwide. Glucocorticoids are a mainstay therapy for asthma because they exert anti-inflammatory effects in multiple lung tissues, including the airway smooth muscle (ASM). However, the mechanism by which glucocorticoids suppress inflammation in ASM remains poorly understood.

Pharmacogenomics: novel loci identification via integrating gene differential analysis and eQTL analysis.

Nearly one-half of asthmatic patients do not respond to the most commonly prescribed controller therapy, inhaled corticosteroids (ICS). We conducted an expression quantitative trait loci (eQTL) analysis using >300 expression microarrays (from 117 lymphoblastoid cell lines) in corticosteroid (dexamethasone) treated and untreated cells derived from asthmatic subjects in the Childhood Asthma Management Program (CAMP) clinical trial. We then tested the associations of eQTL with longitudinal change in airway responsiveness to methacholine (LnPC20) on ICS.