Causal Pathways from Blood Pressure to Larger Qrs Amplitudes a Mendelian Randomization Study

M. Yldau Van Der Ende, Tom Hendriks, Dirk J. Van Veldhuisen, Harold Snieder, Niek Verweij, Pim Van Der Harst*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Abnormal QRS duration and amplitudes on the electrocardiogram are indicative of cardiac pathology and are associated with adverse outcomes. The causal nature of these associations remains uncertain and could be due to QRS abnormalities being a symptom of cardiac damage rather than a factor on the causal pathway. By performing Mendelian randomization (MR) analyses using summary statistics of genome wide association study consortia with sample sizes between 20,687 and 339,224 individuals, we aimed to determine which cardiovascular risk factors causally lead to changes in QRS duration and amplitude (Sokolow-Lyon, Cornell and 12-leadsum products). Additionally, we aimed to determine whether QRS traits have a causal relationship with mortality and longevity. We performed inverse-variance weighted MR as main analyses and MR-Egger regression and weighted median estimation as sensitivity analyses. We found evidence for a causal relationship between higher blood pressure and larger QRS amplitudes (systolic blood pressure on Cornell: 55SNPs, causal effect estimate per 1 mmHg = 9.77 millimeters.milliseconds (SE = 1.38, P = 1.20 x 10(-12)) and diastolic blood pressure on Cornell: 57SNPs, causal effect estimate per 1 mmHg = 14.89 millimeters.milliseconds (SE = 1.82, P = 3.08 x 10(-16)), but not QRS duration. Genetically predicted QRS traits were not associated with longevity, suggesting a more prominent role of acquired factors in explaining the wellknown link between QRS abnormalities and outcome.

Original languageEnglish
Article number5817
Number of pages7
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 11-Apr-2018

Keywords

  • LEFT-VENTRICULAR HYPERTROPHY
  • ACUTE MYOCARDIAL-INFARCTION
  • PROGNOSTIC-SIGNIFICANCE
  • CARDIOVASCULAR EVENTS
  • SYSTOLIC FUNCTION
  • RISK-FACTOR
  • LOCI
  • ELECTROCARDIOGRAM
  • MORTALITY
  • INDIVIDUALS

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