Coronary Artery Disease & Atherosclerosis

Intronic CYP2C9 haplotype tag associated with increased ischemic stroke risk in Asian populations, acting through altered epoxyeicosatrienoic acid (EET) production and impaired cerebrovascular tone regulation

Common intronic variant in the ST3GAL4 sialyltransferase gene associated with modestly elevated VWF antigen and Factor VIII activity levels; the A allele impairs sialic acid capping of these clotting proteins, slowing their hepatic clearance and raising plasma concentrations

Intronic IL6R variant in LD with the IL-6 receptor signaling locus; G allele associates with higher IL-6 pathway activity, elevated CRP, and increased atrial fibrillation risk

Missense variant in ZC3HC1/NIPA altering cell cycle regulation; the T (His363) allele is protective against coronary artery disease (OR 0.90, p=2.4×10⁻¹⁷)

Intronic variant in HNRNPUL1, an RNA-processing gene highly expressed in macrophages and immune cells, associated with elevated early-onset coronary heart disease risk; the common A allele is the risk allele

3' UTR variant in the type 1 deiodinase gene associated with markedly increased cardiac mortality after myocardial infarction, acting through reduced local T4-to-T3 conversion in cardiac tissue

Intronic PDC variant in the phosducin gene — G homozygotes show 12–15 mmHg higher stress-induced blood pressure than A-allele carriers due to reduced sympathetic dampening.

Regulatory variant that increases sortilin expression, lowering LDL cholesterol and cardiovascular risk

Intronic MRAS variant that creates a MEF2 transcription factor binding site in vascular smooth muscle cells, increasing MRAS expression and promoting the pro-atherogenic synthetic phenotype switch linked to coronary artery disease

9p21 locus variant in the ANRIL long non-coding RNA gene associated with intracranial aneurysm and coronary artery disease, with the T allele increasing arterial disease risk across multiple vascular beds

Intronic variant in ANRIL at the 9p21.3 locus — the shared susceptibility region for coronary artery disease and periodontitis; the C allele elevates inflammatory signaling through ANRIL dysregulation and increases susceptibility to aggressive and chronic periodontitis

Intronic variant in the adiponectin gene that influences circulating adiponectin levels, insulin sensitivity, and metabolic response to diet; the T allele is associated with lower adiponectin and higher insulin resistance

Intronic variant in the TGF-beta signaling gene SMAD3 associated with vascular smooth muscle cell regulation and variable coronary artery disease risk across populations

Regulatory variant 80 kb downstream of CXCL12 on chromosome 10q11; the T allele reduces circulating CXCL12 chemokine levels and confers protection against coronary artery disease

Intronic variant in MIA3/TANGO1 affecting collagen secretion and vascular smooth muscle cell behavior, with well-replicated association with coronary artery disease risk

Intronic regulatory variant modulating FURIN expression via allele-specific DNA methylation, associated with coronary artery disease risk and blood pressure through macrophage and endothelial cell mechanisms

Missense variant in the MMP9 fibronectin type II domain affecting matrix metalloproteinase-9 substrate binding; the A allele (Gln279) is associated with altered plaque remodeling dynamics, increased intracranial atherosclerotic stenosis risk, and higher ischemic stroke susceptibility compared with the Arg279 (G allele) form

Intronic M6PR variant associated with modest hypertension risk in East Asian populations through lysosomal trafficking and intracellular receptor recycling pathways

Missense variant in kinesin family member 6; the Arg allele was associated with elevated coronary heart disease risk and with substantially greater benefit from statin therapy in the CARE, WOSCOPS, PROSPER, and PROVE IT-TIMI 22 trials, though a large meta-analysis of 19 case-control studies found no independent CAD risk association

Missense variant in the ABCG2 transporter that impairs membrane localization and alters efflux of drugs, porphyrins, and urate, with the T allele associated with altered antiretroviral drug handling and reduced transporter activity in some cell models

Synonymous exon 2 variant in the adiponectin gene that affects mRNA stability and adiponectin secretion; the G allele is associated with lower circulating adiponectin, higher metabolic syndrome risk, and altered fat distribution

Missense variant in sorting nexin 19 that alters endolysosomal positioning at the ER membrane; the A allele was associated with elevated coronary heart disease risk in a prospective cohort study and confirmed as one of five common risk variants in the ARIC validation

Intergenic variant near IRS1 at 2q36.3 associated with ischemic stroke risk, HDL cholesterol, and adiponectin levels; the A allele is protective

Intronic variant in SNX24 (sorting nexin 24) with roles in vascular endothelial inflammation and platelet alpha-granule biogenesis, including VWF and P-selectin trafficking; G allele is minor and may reduce SNX24 expression efficiency in endothelial and megakaryocyte lineages

Pleiotropic missense variant reducing SH2B3 inhibitory function, increasing blood pressure, CAD risk, platelet count, and susceptibility to autoimmune diseases

Intronic variant in PROX1, the master transcription factor for lymphatic endothelial identity and valve development, associated with increased varicose veins risk through impaired lymphatic-venous drainage

Intronic variant near ST3GAL4 that modulates VWF and Factor VIII sialylation, slowing their hepatic clearance and raising plasma levels — an established independent VTE risk factor

Missense variant in the elastin-crosslinking enzyme LOXL1; the common G allele is one of the strongest known genetic risk factors for exfoliation syndrome and exfoliation glaucoma, a leading cause of secondary glaucoma worldwide

Intronic variant in TNFSF4 (OX40 ligand) linked to a promoter haplotype that reduces OX40L expression; homozygous G carriers show approximately 2-fold increased myocardial infarction risk in some populations, with the strongest signal in women

Promoter variant that disrupts an SP1 transcription factor binding site, increasing MMP-9 expression in vascular tissue; the T allele is associated with elevated plaque instability, higher risk of myocardial infarction, and increased ischemic stroke risk, particularly in Asian populations

Intronic IL6R variant in linkage disequilibrium with the functional Asp358Ala (rs2228145) coding change; the C allele tags a haplotype associated with elevated CRP, LDL, and ApoB and with reduced protection from coronary heart disease risk

Intronic CFDP1 locus variant that regulates BCAR1 expression in vascular tissue via FOXA binding; the A allele reduces BCAR1 levels and is associated with lower carotid intima-media thickness progression and reduced coronary artery disease risk, with the protective effect strongest in women

Independent 9p21.3 CAD risk signal in ANRIL; G allele elevates coronary artery disease risk ~30% per allele and is specifically amplified by sugar-sweetened beverage intake while vegetable intake attenuates risk

Regulatory variant ~80 kb downstream of CXCL12 (SDF-1) associated with elevated plasma CXCL12 levels and increased coronary artery disease risk in European GWAS and replication cohorts

Tag SNP for the ABO blood group locus; T allele marks blood type O (lower clotting proteins), C allele marks non-O types (A, B, AB) with elevated VTE and cardiovascular risk

Intronic SMAD3 variant tagging the CAD-protective haplotype where the T allele reduces SMAD3 enhancer activity in arterial smooth muscle cells, lowering TGF-beta-driven vascular remodeling and coronary artery disease risk

Intronic variant in TC2N (tandem C2 domains, nuclear) robustly associated with venous thromboembolism risk; the T allele increases VTE risk and was validated by CRISPR zebrafish knockdown as a genuine novel hemostasis gene

Missense variant in the ROS1 receptor tyrosine kinase associated with atherothrombotic cardiovascular risk in some populations

Intronic variant in the neuroserpin gene; the A allele has been associated with early-onset ischemic stroke in Caucasian women in an ancestry-specific dominant model

Intronic variant in the mitochondrial folate enzyme MTHFD1L, associated with increased coronary artery disease risk and post-ACS cardiovascular mortality through impaired one-carbon unit supply

Intronic variant near the BOLL gene associated with increased intracranial aneurysm susceptibility, replicated across European, Japanese, and Korean populations.

Intronic variant in DAB2IP associated with increased risk of abdominal aortic aneurysm, myocardial infarction, and peripheral arterial disease through impaired Ras-GTPase regulation and enhanced vascular inflammation

Pathogenic nonsense variant in myocilin causing autosomal dominant juvenile and adult-onset open-angle glaucoma through trabecular meshwork dysfunction and elevated intraocular pressure

Intronic variant in COL27A1 (collagen type XXVII alpha-1) associated with altered connective tissue integrity and elevated varicose vein risk.

Regulatory variant near LOC105378189 non-coding RNA locus on chromosome 14q23; the T allele is associated with increased susceptibility to intracranial berry aneurysm through putative regulatory effects on vascular wall integrity genes

Intronic TSPAN15 variant that modulates ADAM10-mediated shedding of GPVI, the major platelet collagen receptor; the C allele is associated with a 31% increased risk of venous thromboembolism and has pharmacogenomic relevance for emerging anti-GPVI therapies

3' UTR variant near miRNA binding sites in MRAS, associated with ~15% increased coronary artery disease risk through altered vascular smooth muscle cell signaling