Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis

Abstract Coronary artery disease (CAD) genome-wide association studies typically focus on single nucleotide variants (SNVs), and many potentially associated SNVs fail to reach the GWAS significance threshold. We performed gene and pathway-based association (GBA) tests on publicly available Coronary...

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Autores principales:	Praveen Hariharan, Josée Dupuis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80fb5f7535e44446a35b9e00fd67fa3d
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spelling	oai:doaj.org-article:80fb5f7535e44446a35b9e00fd67fa3d2021-12-02T18:50:49ZMapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis10.1038/s41598-021-95637-92045-2322https://doaj.org/article/80fb5f7535e44446a35b9e00fd67fa3d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95637-9https://doaj.org/toc/2045-2322Abstract Coronary artery disease (CAD) genome-wide association studies typically focus on single nucleotide variants (SNVs), and many potentially associated SNVs fail to reach the GWAS significance threshold. We performed gene and pathway-based association (GBA) tests on publicly available Coronary ARtery DIsease Genome wide Replication and Meta-analysis consortium Exome (n = 120,575) and multi ancestry pan UK Biobank study (n = 442,574) summary data using versatile gene-based association study (VEGAS2) and Multi-marker analysis of genomic annotation (MAGMA) to identify novel genes and pathways associated with CAD. We included only exonic SNVs and excluded regulatory regions. VEGAS2 and MAGMA ranked genes and pathways based on aggregated SNV test statistics. We used Bonferroni corrected gene and pathway significance threshold at 3.0 × 10–6 and 1.0 × 10–5, respectively. We also report the top one percent of ranked genes and pathways. We identified 17 top enriched genes with four genes (PCSK9, FAM177, LPL, ARGEF26), reaching statistical significance (p ≤ 3.0 × 10–6) using both GBA tests in two GWAS studies. In addition, our analyses identified ten genes (DUSP13, KCNJ11, CD300LF/RAB37, SLCO1B1, LRRFIP1, QSER1, UBR2, MOB3C, MST1R, and ABCC8) with previously unreported associations with CAD, although none of the single SNV associations within the genes were genome-wide significant. Among the top 1% non-lipid pathways, we detected pathways regulating coagulation, inflammation, neuronal aging, and wound healing.Praveen HariharanJosée DupuisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Praveen Hariharan Josée Dupuis Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
description	Abstract Coronary artery disease (CAD) genome-wide association studies typically focus on single nucleotide variants (SNVs), and many potentially associated SNVs fail to reach the GWAS significance threshold. We performed gene and pathway-based association (GBA) tests on publicly available Coronary ARtery DIsease Genome wide Replication and Meta-analysis consortium Exome (n = 120,575) and multi ancestry pan UK Biobank study (n = 442,574) summary data using versatile gene-based association study (VEGAS2) and Multi-marker analysis of genomic annotation (MAGMA) to identify novel genes and pathways associated with CAD. We included only exonic SNVs and excluded regulatory regions. VEGAS2 and MAGMA ranked genes and pathways based on aggregated SNV test statistics. We used Bonferroni corrected gene and pathway significance threshold at 3.0 × 10–6 and 1.0 × 10–5, respectively. We also report the top one percent of ranked genes and pathways. We identified 17 top enriched genes with four genes (PCSK9, FAM177, LPL, ARGEF26), reaching statistical significance (p ≤ 3.0 × 10–6) using both GBA tests in two GWAS studies. In addition, our analyses identified ten genes (DUSP13, KCNJ11, CD300LF/RAB37, SLCO1B1, LRRFIP1, QSER1, UBR2, MOB3C, MST1R, and ABCC8) with previously unreported associations with CAD, although none of the single SNV associations within the genes were genome-wide significant. Among the top 1% non-lipid pathways, we detected pathways regulating coagulation, inflammation, neuronal aging, and wound healing.
format	article
author	Praveen Hariharan Josée Dupuis
author_facet	Praveen Hariharan Josée Dupuis
author_sort	Praveen Hariharan
title	Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
title_short	Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
title_full	Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
title_fullStr	Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
title_full_unstemmed	Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis
title_sort	mapping gene and gene pathways associated with coronary artery disease: a cardiogram exome and multi-ancestry uk biobank analysis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/80fb5f7535e44446a35b9e00fd67fa3d
work_keys_str_mv	AT praveenhariharan mappinggeneandgenepathwaysassociatedwithcoronaryarterydiseaseacardiogramexomeandmultiancestryukbiobankanalysis AT joseedupuis mappinggeneandgenepathwaysassociatedwithcoronaryarterydiseaseacardiogramexomeandmultiancestryukbiobankanalysis
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Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis

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