Your cardiovascular genetic risk profile extends far beyond cholesterol levels, and much of it won't appear on a standard lipid panel.
Lipoprotein(a), LDL cholesterol genes, the 9p21 locus, endothelial nitric oxide, statin and warfarin pharmacogenomics, thrombophilia, and hereditary hemochromatosis. 16 variants across the cardiovascular system.
The Biology
Some cardiovascular risk factors do not show up on routine bloodwork. Lipoprotein(a), an LDL-like particle linked to atherosclerosis through a pathway separate from LDL cholesterol, is largely genetically determined and is not part of a standard lipid panel. The 9p21 locus is associated with coronary artery disease risk independent of cholesterol levels. Endothelial nitric oxide production, the response to statins and warfarin, and inherited clotting risk all have genetic components as well.
What Varia Analyzes
16 variants. LPA, the lipoprotein(a) gene (rs10455872, rs3798220); PCSK9 R46L (rs11591147), a loss-of-function variant associated with lower LDL cholesterol; LDLR (rs6511720) and APOB (rs693), both LDL cholesterol loci; CDKN2B-AS1 at the 9p21 coronary artery disease locus (rs1333049, rs10757278); NOS3, endothelial nitric oxide synthase, at Glu298Asp (rs1799983) and the -786T/C promoter (rs2070744); SLCO1B1 V174A (rs4149056), statin-associated myopathy; VKORC1 (rs9923231), warfarin sensitivity; FADS1 (rs174537), omega-3 conversion efficiency; F5 Factor V Leiden (rs6025) and F2 Prothrombin G20210A (rs1799963), inherited thrombophilia variants; and HFE C282Y (rs1800562) and H63D (rs1799945), the common hereditary hemochromatosis variants.
Why It Matters
Several of these have published clinical guidance. CPIC, the Clinical Pharmacogenetics Implementation Consortium, publishes guidelines that use SLCO1B1 genotype for statin prescribing and VKORC1 genotype for warfarin dosing. Lipoprotein(a) is not measured in a standard lipid panel, so the LPA variants point to a measurement many people have never had. Two copies of HFE C282Y is the primary genetic cause of hereditary hemochromatosis, which can lead to iron overload over time. These are findings to discuss with a clinician, not instructions.
Polygenic Risk Scores
Varia's catalog covers single-variant cardiovascular findings. Polygenic risk scores (PRS) combine hundreds or thousands of variants into a population-level CAD estimate. Varia publishes an editorial entry on published CAD scores, what cardiology authorities say about them, and where a clinically validated result comes from. Varia does not compute a per-user PRS from a consumer file. See Polygenic Risk Scores.
Key Sources
- Clarke R, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009.
- Cohen JC, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006.
- Helgadottir A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007.
- SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy. A genomewide study. N Engl J Med. 2008.
- Feder JN, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996.