# Population-based pharmacogenomic assessment of QT prolongation

> **NIH NIH R01** · KAISER FOUNDATION RESEARCH INSTITUTE · 2021 · $754,578

## Abstract

Abstract
Cardiotoxicity of commonly prescribed medications, typically assessed by electrocardiographic features such
as prolongation of the QT interval, is a relevant clinical topic because it has regulatory consequences (labelling
and withdrawal of drugs) and is associated with potentially fatal patient-level outcomes (ventricular arrhythmias
and Torsade de Pointes). We propose here to leverage the extensive phenotypic and genotypic data resources
of the Kaiser Permanente Northern California (KPNC) Research Program on Genes, Environment and Health
(RPGEH), and the ability to link these data to other health plan databases, namely our pharmacy,
electrocardiogram (ECG) and outpatient/inpatient utilization databases. In particular, we will use the Genetic
Epidemiology Research in Adult Health and Aging (GERA) cohort members (n=110,266; n=69,276 with 1 or
more available ECGs; 52,667 with two or more ECGs). Our ability to conduct longitudinal analyses of the QT
interval over up to 20 years in a large and ethnically diverse population (The GERA cohort is 78% Caucasian,
6% Asian/Pacific Islander, 6% Latino, 3% African-American, 5% other or mixed) and to identify and
characterize genetic loci that influence adverse drug reactions is unique and will advance our understanding of
the genetic basis of cardiac toxicity of commonly prescribed medications. Replication of findings in Europeans
will be sought in 70,944 Caucasian subjects with ECG, genome-wide and medication data in the UK Biobank.
We will perform functional annotation of replicated hits to shed light on biological pathways and tissues
involved. In addition, to complement this approach and to more fully address the downstream clinical
significance of QT prolongation, we will also examine: a) genetic predictors of incident ventricular arrhythmias
and of Torsade de Pointes; b) whether the identified gene by drug interactions are associated with these
adverse outcomes and c) degree of mediation by QTc prolongation. Our results will be shared with the
Pharmacogenomics Research Network (PGRN) for replication and meta-analytical purposes. Our long-term
goal is to advance the field of the genetic basis of drug cardiotoxicity and its downstream
consequences that will inform therapeutic considerations.

## Key facts

- **NIH application ID:** 10147138
- **Project number:** 5R01HL140924-04
- **Recipient organization:** KAISER FOUNDATION RESEARCH INSTITUTE
- **Principal Investigator:** Carlos Iribarren
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $754,578
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147138

## Citation

> US National Institutes of Health, RePORTER application 10147138, Population-based pharmacogenomic assessment of QT prolongation (5R01HL140924-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147138. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*