학술논문
Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes
Document Type
article
Author
Halford, Jennifer L; Morrill, Valerie N; Choi, Seung Hoan; Jurgens, Sean J; Melloni, Giorgio; Marston, Nicholas A; Weng, Lu-Chen; Nauffal, Victor; Hall, Amelia W; Gunn, Sophia; Austin-Tse, Christina A; Pirruccello, James P; Khurshid, Shaan; Rehm, Heidi L; Benjamin, Emelia J; Boerwinkle, Eric; Brody, Jennifer A; Correa, Adolfo; Fornwalt, Brandon K; Gupta, Namrata; Haggerty, Christopher M; Harris, Stephanie; Heckbert, Susan R; Hong, Charles C; Kooperberg, Charles; Lin, Henry J; Loos, Ruth JF; Mitchell, Braxton D; Morrison, Alanna C; Post, Wendy; Psaty, Bruce M; Redline, Susan; Rice, Kenneth M; Rich, Stephen S; Rotter, Jerome I; Schnatz, Peter F; Soliman, Elsayed Z; Sotoodehnia, Nona; Wong, Eugene K; Sabatine, Marc S; Ruff, Christian T; Lunetta, Kathryn L; Ellinor, Patrick T; Lubitz, Steven A
Source
Nature Communications. 13(1)
Subject
Language
Abstract
Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P