Genome-wide association study of absolute QRS voltage identifies common variants of TBX3 as genetic determinants of left ventricular mass in a healthy Japanese population

Japan Pharmacogenomics Data Science Consortium (JPDSC)

Research output: Contribution to journalArticle

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Abstract

Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 in TBX3|MED13L with a 0.071 mV (95% CI, 0.038-0.11 mV) shorter R wave amplitude in the V5 lead per minor allele copy (P = 7.635 × 10-8). The transcriptional repressor, TBX3, is proposed to suppress the development of working ventricular myocardium. Our findings suggest that genetic variation of Tbx3 is associated with LV mass in a healthy Japanese population.

Original languageEnglish
Article numbere0155550
JournalPLoS One
Volume11
Issue number5
DOIs
Publication statusPublished - 2016 May 1

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Genome-Wide Association Study
Genes
Single Nucleotide Polymorphism
Electric potential
pharmacogenomics
Population
Radio Waves
Gene encoding
Pharmacogenetics
Left Ventricular Hypertrophy
heart failure
myocardium
hypertrophy
meta-analysis
Computer Simulation
volunteers
Meta-Analysis
Myocardium
Healthy Volunteers
Japan

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genome-wide association study of absolute QRS voltage identifies common variants of TBX3 as genetic determinants of left ventricular mass in a healthy Japanese population. / Japan Pharmacogenomics Data Science Consortium (JPDSC).

In: PLoS One, Vol. 11, No. 5, e0155550, 01.05.2016.

Research output: Contribution to journalArticle

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