Evidence map›Paper›PMID 36271874›Full record

SynthesisGenetics2022

A large genome-wide association study of QT interval length utilizing electronic health records.

Thomas J Hoffmann, Meng Lu, Akinyemi Oni-Orisan, Catherine Lee, Neil Risch, Carlos Iribarren

Abstract readMeta-Analysis
In one paragraph

Synthesis in Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  5. Genome-wide association study-identified novel genetic loci for QT interval in Taiwan: implications for population-specific arrhythmia risk.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Thomas J HoffmannInstitute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-6893-4449
Meng LuDivision of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.ORCID 0000-0002-9116-0020
Akinyemi Oni-OrisanInstitute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0002-5897-5543
Catherine LeeDivision of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.ORCID 0000-0003-0008-9052
Neil RischInstitute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0002-4126-2061
Carlos IribarrenDivision of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.ORCID 0000-0001-5622-1839

Funding

A Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8M
Population-based pharmacogenomic assessment of QT prolongationR01HL140924 · NHLBI · KAISER FOUNDATION RESEARCH INSTITUTE · PI IRIBARREN, CARLOS · 2018 to 2021
$3.0M
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHLBI NIH HHS R01 HL140924NIA NIH HHS RC2 AG036607
6 · The paper itself

Abstract

QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants. Conditional analysis identified 15 additional variants, 3 of which were novel. Little, if any, difference was seen when adjusting for putative QT interval lengthening medications genome-wide. Using multiple measurements in Genetic Epidemiology Research on Adult Health and Aging increased variance explained by 163%, and we show that the ≈6 measurements in Genetic Epidemiology Research on Adult Health and Aging was equivalent to a 2.4× increase in sample size of a design with a single measurement. The array heritability was estimated at ≈17%, approximately half of our estimate of 36% from family correlations. Heritability enrichment was estimated highest and most significant in cardiovascular tissue (enrichment 7.2, 95% CI = 5.7-8.7, P = 2.1e-10), and many of the novel variants included expression quantitative trait loci in heart and other relevant tissues. Comparing our results to other cardiac function traits, it appears that QT interval has a multifactorial genetic etiology.

Indexed as

Electronic Health RecordsGenome-Wide Association StudyAdultHumansPhenotypePolymorphism, Single NucleotideQuantitative Trait Locielectronic health recordsgenome-wide association studymedicationQT intervalrepeated measurements

Identifiers

PMID36271874
PMCPMC9713425

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.