Oligogenic Architecture of Rare Noncoding Variants Distinguishes 4 Congenital Heart Disease Phenotypes
Jan 1, 2023·,,,,,,,,,,,,,,,,,,,,,,,,,,·
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MD James R. Priest
PhD Mengyao Yu
Matthew Aguirre
PhD Meiwen Jia
BS Ketrin Gjoni
PhD Aldo Cordova-Palomera
BS Chad Munger
PhD Dulguun Amgalan
MD PhD Alexandre Pereira
Dvm Catherine Tcheandjieu
PhD Christine Seidman
M. Seidman
PhD Martin Tristani-Firouzi
Priya Md
MC Srivastava
Milan Loos
P. Chami
P. Cordell
PhD Martina Dreßen
PhD Bertram Mueller-Myhsok
PhD Harald Lahm
PhD Markus Krane
Macy Pollard
PhD Jesse M. Engreitz
PhD Sarah A. Gagliano Taliun
PhD Bruce D. Gelb
M. Priest
Abstract
Background: Congenital heart disease (CHD) is highly heritable, but the power to identify inherited risk has been limited to analyses of common variants in small cohorts. Methods: We performed reimputation of 4 CHD cohorts (n=55 342) to the TOPMed reference panel (freeze 5), permitting meta-analysis of 14 784 017 variants including 6 035 962 rare variants of high imputation quality as validated by whole genome sequencing. Results: Meta-analysis identified 16 novel loci, including 12 rare variants, which displayed moderate or large effect sizes (median odds ratio, 3.02) for 4 separate CHD categ…
Type
Publication
Circulation: Genomic and Precision Medicine