PMID- 33574266
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210225
IS  - 2056-7944 (Electronic)
IS  - 2056-7944 (Linking)
VI  - 6
IP  - 1
DP  - 2021 Feb 11
TI  - Convergence of biomarkers and risk factor trait loci of coronary artery disease 
      at 3p21.31 and HLA region.
PG  - 12
LID - 10.1038/s41525-021-00174-z [doi]
LID - 12
AB  - 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.
FAU - Nikpay, Majid
AU  - Nikpay M
AUID- ORCID: 0000-0003-0285-6454
AD  - Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart 
      Institute, Ottawa, ON, Canada. mnikpay@ottawaheart.ca.
FAU - McPherson, Ruth
AU  - McPherson R
AD  - Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart 
      Institute, Ottawa, ON, Canada. rmcpherson@ottawaheart.ca.
AD  - Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON, 
      Canada. rmcpherson@ottawaheart.ca.
LA  - eng
GR  - FDN-154308/Gouvernement du Canada | Canadian Institutes of Health Research 
      (Instituts de Recherche en Sante du Canada)/
PT  - Journal Article
DEP - 20210211
PL  - England
TA  - NPJ Genom Med
JT  - NPJ genomic medicine
JID - 101685193
PMC - PMC7878768
COIS- The authors declare no competing interests.
EDAT- 2021/02/13 06:00
MHDA- 2021/02/13 06:01
PMCR- 2021/02/11
CRDT- 2021/02/12 05:56
PHST- 2020/07/30 00:00 [received]
PHST- 2021/01/06 00:00 [accepted]
PHST- 2021/02/12 05:56 [entrez]
PHST- 2021/02/13 06:00 [pubmed]
PHST- 2021/02/13 06:01 [medline]
PHST- 2021/02/11 00:00 [pmc-release]
AID - 10.1038/s41525-021-00174-z [pii]
AID - 174 [pii]
AID - 10.1038/s41525-021-00174-z [doi]
PST - epublish
SO  - NPJ Genom Med. 2021 Feb 11;6(1):12. doi: 10.1038/s41525-021-00174-z.