Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region

Abstract Here we seek to identify molecular biomarkers that mediate the effect of risk factors on coronary artery disease (CAD). We perform a SNP-based multiomics data analysis to find biomarkers (probes) causally associated with the risk of CAD within known genomic loci for its risk factors. We ide...

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Autores principales:	Majid Nikpay, Ruth McPherson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/269ba157c6084399b81c395f5ea2daea
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spelling	oai:doaj.org-article:269ba157c6084399b81c395f5ea2daea2021-12-02T12:09:18ZConvergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region10.1038/s41525-021-00174-z2056-7944https://doaj.org/article/269ba157c6084399b81c395f5ea2daea2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00174-zhttps://doaj.org/toc/2056-7944Abstract Here we seek to identify molecular biomarkers that mediate the effect of risk factors on coronary artery disease (CAD). We perform a SNP-based multiomics data analysis to find biomarkers (probes) causally associated with the risk of CAD within known genomic loci for its risk factors. We identify 78 biomarkers, the majority (64%) of which are methylation probes. We detect the convergence of several CNS and lifestyle trait loci and their biomarkers at the 3p21.31 and human leukocyte antigen (HLA) regions. The 3p21.31 locus was the most populated region in the convergence of biomarkers and risk factors. In this region, we noted as the BSN gene becomes methylated the level of stomatin (STOM) in blood increases and this contributes to higher risk of CAD. In the HLA locus, we identify several methylation biomarkers associated with various CAD risk factors. SNPs in the CFB gene display a trans-regulatory impact on the GRIA4 protein level. A methylation site upstream of the APOE gene is associated with a higher protein level of S100A13 which in turn leads to higher LDL-C and greater CAD risk. We find UHRF1BP1 and ILRUN mediate the effect of obesity on CAD whereas methylation sites within NOS3 and CKM mediate the effect of their associated-risk factors on CAD. This study provides further insight into the biology of CAD and identifies a list of biomarkers that mediate the impact of risk factors on CAD. A SNP-based initiative can unite data from various fields of omics into a single network of knowledge.Majid NikpayRuth McPhersonNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Majid Nikpay Ruth McPherson Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region
description	Abstract Here we seek to identify molecular biomarkers that mediate the effect of risk factors on coronary artery disease (CAD). We perform a SNP-based multiomics data analysis to find biomarkers (probes) causally associated with the risk of CAD within known genomic loci for its risk factors. We identify 78 biomarkers, the majority (64%) of which are methylation probes. We detect the convergence of several CNS and lifestyle trait loci and their biomarkers at the 3p21.31 and human leukocyte antigen (HLA) regions. The 3p21.31 locus was the most populated region in the convergence of biomarkers and risk factors. In this region, we noted as the BSN gene becomes methylated the level of stomatin (STOM) in blood increases and this contributes to higher risk of CAD. In the HLA locus, we identify several methylation biomarkers associated with various CAD risk factors. SNPs in the CFB gene display a trans-regulatory impact on the GRIA4 protein level. A methylation site upstream of the APOE gene is associated with a higher protein level of S100A13 which in turn leads to higher LDL-C and greater CAD risk. We find UHRF1BP1 and ILRUN mediate the effect of obesity on CAD whereas methylation sites within NOS3 and CKM mediate the effect of their associated-risk factors on CAD. This study provides further insight into the biology of CAD and identifies a list of biomarkers that mediate the impact of risk factors on CAD. A SNP-based initiative can unite data from various fields of omics into a single network of knowledge.
format	article
author	Majid Nikpay Ruth McPherson
author_facet	Majid Nikpay Ruth McPherson
author_sort	Majid Nikpay
title	Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region
title_short	Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region
title_full	Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region
title_fullStr	Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region
title_full_unstemmed	Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region
title_sort	convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and hla region
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/269ba157c6084399b81c395f5ea2daea
work_keys_str_mv	AT majidnikpay convergenceofbiomarkersandriskfactortraitlociofcoronaryarterydiseaseat3p2131andhlaregion AT ruthmcpherson convergenceofbiomarkersandriskfactortraitlociofcoronaryarterydiseaseat3p2131andhlaregion
_version_	1718394679445159936

Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region

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