학술논문
Multi-Ethnic Genome-Wide Association Study of Decomposed Cardioelectric Phenotypes Illustrates Strategies to Identify and Characterize Evidence of Shared Genetic Effects for Complex Traits
Document Type
article
Author
Baldassari, Antoine R; Sitlani, Colleen M; Highland, Heather M; Arking, Dan E; Buyske, Steve; Darbar, Dawood; Gondalia, Rahul; Graff, Misa; Guo, Xiuqing; Heckbert, Susan R; Hindorff, Lucia A; Hodonsky, Chani J; Ida Chen, Yii-Der; Kaplan, Robert C; Peters, Ulrike; Post, Wendy; Reiner, Alex P; Rotter, Jerome I; Shohet, Ralph V; Seyerle, Amanda A; Sotoodehnia, Nona; Tao, Ran; Taylor, Kent D; Wojcik, Genevieve L; Yao, Jie; Kenny, Eimear E; Lin, Henry J; Soliman, Elsayed Z; Whitsel, Eric A; North, Kari E; Kooperberg, Charles; Avery, Christy L
Source
Circulation Genomic and Precision Medicine. 13(4)
Subject
Language
Abstract
BackgroundWe examined how expanding electrocardiographic trait genome-wide association studies to include ancestrally diverse populations, prioritize more precise phenotypic measures, and evaluate evidence for shared genetic effects enabled the detection and characterization of loci.MethodsWe decomposed 10 seconds, 12-lead electrocardiograms from 34 668 multi-ethnic participants (15% Black; 30% Hispanic/Latino) into 6 contiguous, physiologically distinct (P wave, PR segment, QRS interval, ST segment, T wave, and TP segment) and 2 composite, conventional (PR interval and QT interval) interval scale traits and conducted multivariable-adjusted, trait-specific univariate genome-wide association studies using 1000-G imputed single-nucleotide polymorphisms. Evidence of shared genetic effects was evaluated by aggregating meta-analyzed univariate results across the 6 continuous electrocardiographic traits using the combined phenotype adaptive sum of powered scores test.ResultsWe identified 6 novels (CD36, PITX2, EMB, ZNF592, YPEL2, and BC043580) and 87 known loci (adaptive sum of powered score test P