Student and Faculty Publications

Authors

Krishna G Aragam
Tao Jiang
Anuj Goel
Stavroula Kanoni
Brooke N Wolford
Deepak S Atri
Elle M Weeks
Minxian Wang
George Hindy
Wei Zhou
Christopher Grace
Carolina Roselli
Nicholas A Marston
Frederick K Kamanu
Ida Surakka
Loreto Muñoz Venegas
Paul Sherliker
Satoshi Koyama
Kazuyoshi Ishigaki
Bjørn O Åsvold
Michael R Brown
Ben Brumpton
Paul S de Vries
Olga Giannakopoulou
Panagiota Giardoglou
Daniel F Gudbjartsson
Ulrich Güldener
Syed M Ijlal Haider
Anna Helgadottir
Maysson Ibrahim
Adnan Kastrati
Thorsten Kessler
Theodosios Kyriakou
Tomasz Konopka
Ling Li
Lijiang Ma
Thomas Meitinger
Sören Mucha
Matthias Munz
Federico Murgia
Jonas B Nielsen
Markus M Nöthen
Shichao Pang
Tobias Reinberger
Gavin Schnitzler
Damian Smedley
Gudmar Thorleifsson
Moritz von Scheidt
Jacob C Ulirsch
Biobank Japan
EPIC-CVD
David O Arnar
Noël P Burtt
Maria C Costanzo
Jason Flannick
Kaoru Ito
Dong-Keun Jang
Yoichiro Kamatani
Amit V Khera
Issei Komuro
Iftikhar J Kullo
Luca A Lotta
Christopher P Nelson
Robert Roberts
Gudmundur Thorgeirsson
Unnur Thorsteinsdottir
Thomas R Webb
Aris Baras
Johan L M Björkegren
Eric Boerwinkle
George Dedoussis
Hilma Holm
Kristian Hveem
Olle Melander
Alanna C Morrison
Marju Orho-Melander
Loukianos S Rallidis
Arno Ruusalepp
Marc S Sabatine
Kari Stefansson
Pierre Zalloua
Patrick T Ellinor
Martin Farrall
John Danesh
Christian T Ruff
Hilary K Finucane
Jemma C Hopewell
Robert Clarke
Rajat M Gupta
Jeanette Erdmann
Nilesh J Samani
Heribert Schunkert
Hugh Watkins
Cristen J Willer
Panos Deloukas
Sekar Kathiresan
Adam S Butterworth
CARDIoGRAMplusC4D Consortium

Publication Date

12-1-2022

Journal

Nature Genetics

Abstract

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR-Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.

Keywords

Humans, Coronary Artery Disease, Genome-Wide Association Study

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