Research — GeneOps

rs1800788 Upstream promoter variant in fibrinogen beta chain that increases IL-6-driven FGB transcription, raising plasma fibrinogen levels and amplifying cardiovascular and thrombotic risk

Chromosome 4 Risk Allele T Category Coagulation & Clotting Factors Tags Blood Clotting, Cardiovascular, Inflammation, Thrombosis, Atherosclerosis, Thrombophilia

Plasma fibrinogen is both the raw material for blood clots and a sensitive index of systemic inflammation. Every 1 g/L increase in fibrinogen(https://pubmed.ncbi.nlm.nih.gov/16219884/) doubles the hazard for coronary heart disease and nearly doubles it for ischemic stroke across 154,211 participants in the...

rs1805794 Component of the MRN complex essential for DNA double-strand break repair, telomere maintenance, and cell cycle checkpoint signaling; this variant alters the BRCT domain and modestly impairs DNA damage response

Chromosome 8 Risk Allele G Category Cancer Risk Tags Cancer Risk, DNA Repair, Double-Strand Break Repair, Cancer Screening

Every day, your cells sustain tens of thousands of DNA lesions from normal metabolism, environmental exposures, and replication errors. Most are single-strand nicks that are easily patched. But the most dangerous lesions are double-strand breaks (DSBs)(), which sever both strands of the helix simultaneously. The...

rs1861494 Intronic IFNG variant that modulates interferon-gamma expression, with the T allele linked to elevated IFN-γ secretion, greater IBD disease severity, and altered susceptibility to tuberculosis and other immune-mediated conditions

Chromosome 12 Risk Allele T Category Interferon Signaling & Systemic Autoimmune Tags Autoimmune, Inflammation, Interferon, Immune Function, Inflammatory Bowel Disease, Infection Risk

Interferon-gamma is the immune system's master activator — the cytokine that tells macrophages to destroy intracellular pathogens, drives Th1 polarization(https://pubmed.ncbi.nlm.nih.gov/25171510/), and keeps chronic inflammatory responses calibrated against genuine threats. rs1861494 is an intronic polymorphism in...

rs1883832 Kozak sequence variant at position −1 of the CD40 start codon — the C allele boosts translational efficiency, producing ~30% more CD40 protein and increasing susceptibility to Graves' disease; the T allele reduces CD40 expression and independently elevates risk for multiple sclerosis and Crohn's disease

Chromosome 20 Risk Allele C Category B-Cell Immunity & Antibody-Mediated Disease Tags Immune & Autoimmune, B-Cell Signaling, Thyroid, Autoimmune, Inflammation

The CD40 gene encodes a co-stimulatory receptor(https://omim.org/entry/109535) that sits at the intersection of innate and adaptive immunity. When CD40 on an antigen-presenting cell binds its ligand CD40L (CD154) on activated T helper cells, it triggers B-cell proliferation, immunoglobulin class switching, germinal...

rs2131925 Intronic tag SNP in the DOCK7/ANGPTL3 region; the T allele is associated with higher fasting triglycerides, higher LDL cholesterol, and elevated cardiovascular risk through reduced ANGPTL3-pathway LPL activity

Chromosome 1 Risk Allele T Category Atherogenic Lipoproteins Tags Triglycerides, Cardiovascular, Fat Metabolism, Heart Disease, LDL Cholesterol

Your blood lipid levels after a meal depend on how efficiently lipoprotein lipase (LPL) — the enzyme that dismantles triglyceride-rich VLDL and chylomicron particles — can do its job. One of LPL's main regulators is ANGPTL3(https://pubmed.ncbi.nlm.nih.gov/20686565/). The rs2131925 variant sits in a nearby gene...

rs225015 3' UTR regulatory variant in DIO2 that may alter local thyroid hormone availability, influencing how the body responds to levothyroxine therapy and how well inactive T4 is converted to active T3 in tissues

Chromosome 14 Risk Allele A Category Vitamin D Metabolism Tags Thyroid, Hormones & Thyroid, Selenium, Micronutrients, Vitamins

The DIO2 gene encodes type II iodothyronine deiodinase(https://pubmed.ncbi.nlm.nih.gov/36206932/), the enzyme responsible for locally activating thyroid hormone in the brain, heart, muscle, and pituitary gland. The thyroid itself secretes mostly T4 (thyroxine), which is biologically inert until converted to T3...

rs2277339 Missense variant in PRIM1 (DNA primase small subunit) that changes aspartate to alanine at position 5 of the protein; the G allele (Asp5Ala) is associated with later age at natural menopause by approximately 0.35 years per copy, implicating DNA replication priming fidelity in the rate of ovarian follicle depletion

Chromosome 12 Risk Allele T Category Gamete Quality & DNA Repair Tags Ovarian Reserve, Fertility, Reproductive Health, Menopause, DNA Repair, Aging

Every cell in your body replicates approximately 6 billion base pairs of DNA during each division cycle. Before a new DNA strand can be synthesised, a molecular machine called DNA primase(https://pubmed.ncbi.nlm.nih.gov/22267201/) must first lay down short RNA primers at thousands of sites. PRIM1 encodes the small...

rs2294918 Second PNPLA3 missense variant that reduces hepatic PNPLA3 mRNA and protein expression by ~50%, independently associated with NAFLD and elevated liver enzymes, and modifies the risk conferred by the co-located I148M variant (rs738409).

Chromosome 22 Risk Allele A Category Liver Fat Tags Fat Metabolism, Liver Health, Liver Disease, Cancer Risk, Alcohol

Most people who know about PNPLA3 genetics know about rs738409 (I148M) — the strongest common genetic risk factor for fatty liver disease. But PNPLA3 harbours a second functionally important variant, rs2294918, that acts not by changing the protein's enzyme activity but by changing how much of the protein the liver...

rs2738058 Intergenic variant downstream of the DEFA1A3 alpha-defensin locus; T risk allele is associated with a 28% increased risk of periodontitis through altered neutrophil defensin availability in the gingival immune response

Chromosome 8 Risk Allele T Category Dental & Oral Health Tags Dental & Oral Health, Innate Immunity, Inflammation, Omega-3, Immune System

Periodontitis — the inflammatory destruction of the bone and tissue supporting teeth — is far more than a dental hygiene problem. It is a systemic inflammatory disease with a strong genetic component(https://pubmed.ncbi.nlm.nih.gov/20403110/), and variants in the innate immune response play a central role. The...

rs28937319 Rare loss-of-function missense variant in the cardiac sodium channel Nav1.5 causing congenital sick sinus syndrome through altered channel inactivation kinetics; also reported in association with Brugada syndrome and dilated cardiomyopathy

Chromosome 3 Risk Allele A Category Arrhythmia & Heart Rhythm Tags Arrhythmia, Heart Disease, Cardiovascular, Genetic Counseling, Carrier Status

Every heartbeat begins in the sinoatrial node (SAN), a cluster of specialized pacemaker cells that fire spontaneously and propagate an electrical impulse through the atria and into the ventricles. That propagation depends on Nav1.5(https://pubmed.ncbi.nlm.nih.gov/29798782/), the sodium channel encoded by SCN5A. The...