Updating probability of pathogenicity for RYR1 and CACNA1S exon variants in individuals without malignant hyperthermia after exposure to triggering anesthetics.

Objectives: We aimed to classify genetic variants in RYR1 and CACNA1S associated with malignant hyperthermia using biobank genotyping data in patients exposed to triggering anesthetics without malignant hyperthermia phenotype.

Methods: We identified individuals who underwent surgery and were exposed to triggering anesthetics without malignant hyperthermia phenotype and who had RYR1 or CACNA1S genotyping data available in our biobank. We classified all variants in the cohort using a Bayesian framework of the American College of Medical Genetics and Genomics and the Association of Molecular Pathologists guidelines for variant classification and updated the posterior probabilities from this model with the new information from our biobank cohort.

Genome-Wide Approach to Measure Variant-Based Heritability of Drug Outcome Phenotypes.

Pharmacogenomic studies have successfully identified variants-typically with large effect sizes in drug target and metabolism enzymes-that predict drug outcome phenotypes. However, these variants may account for a limited proportion of phenotype variability attributable to the genome. Using genome-wide common variation, we measured the narrow-sense heritability ( ) of seven pharmacodynamic and five pharmacokinetic phenotypes across three cardiovascular drugs, two antibiotics, and three immunosuppressants.

Evidence for Pharmacogenomic Effects on Risperidone Outcomes in Pediatrics.

Objective: To determine the association between genetic variants reported to affect risperidone and adverse events (AEs) in children and adolescents.

Methods: Individuals aged 18 years or younger with ≥4 weeks of risperidone exposure in a deidentified DNA biobank were included. The primary outcome was AE frequency as a function of genotype.

Pharmacogenetics to Predict Adverse Events Associated With Antidepressants.

Objectives: To determine the association between cytochrome P450 2C19 (CYP2C19) metabolizer status and risk for escitalopram and citalopram, collectively termed (es)citalopram, and sertraline adverse events (AEs) in children.

Methods: In this retrospective cohort study, we used deidentified electronic health records linked to DNA. The cohort included children ≤18 years with ≥2 days of (es)citalopram or ≥7 days of sertraline exposure.

Acute Kidney Injury During Treatment with Intravenous Acyclovir for Suspected or Confirmed Neonatal Herpes Simplex Virus Infection.

Objective: To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants.

Study Design: We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age <60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included.

CYP2D6 genotype and adverse events to risperidone in children and adolescents.

Background: There are few and conflicting data on the role of cytochrome P450 2D6 (CYP2D6) polymorphisms in relation to risperidone adverse events (AEs) in children. This study assessed the association between CYP2D6 metabolizer status and risk for risperidone AEs in children.

Methods: Children ≤18 years with at least 4 weeks of risperidone exposure were identified using BioVU, a de-identified DNA biobank linked to electronic health record data.