Instrumental variable and colocalization analyses identify endotrophin and HTRA1 as potential therapeutic targets for coronary artery disease.

Autor:	Lee PC; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Jung IH; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Thussu S; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Patel V; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Wagoner R; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Burks KH; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Amrute J; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Elenbaas JS; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Kang CJ; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO 63108, USA., Young EP; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO 63108, USA., Scherer PE; Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Stitziel NO; Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO 63108, USA.; Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 May 24; Vol. 27 (7), pp. 110104. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110104
Abstrakt:	Coronary artery disease (CAD) remains a leading cause of disease burden globally, and there is a persistent need for new therapeutic targets. Instrumental variable (IV) and genetic colocalization analyses can help identify novel therapeutic targets for human disease by nominating causal genes in genome-wide association study (GWAS) loci. We conducted cis-IV analyses for 20,125 genes and 1,746 plasma proteins with CAD using molecular trait quantitative trait loci variant (QTLs) data from three different studies. 19 proteins and 119 genes were significantly associated with CAD risk by IV analyses and demonstrated evidence of genetic colocalization. Notably, our analyses validated well-established targets such as PCSK9 and ANGPTL4 while also identifying HTRA1 and endotrophin (a cleavage product of COL6A3) as proteins whose levels are causally associated with CAD risk. Further experimental studies are needed to confirm the causal role of the genes and proteins identified through our multiomic cis-IV analyses on human disease. Competing Interests: N.O.S. has received consulting fees from Novo Nordisk. The other authors have no conflicts. (© 2024 The Author(s).)
Databáze:	MEDLINE
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