Research — GeneOps

rs582757 Intronic regulatory variant in TNFAIP3 — the primary NF-kB brake gene — with the C allele independently increasing psoriasis susceptibility (OR 1.23) and showing pleiotropic associations across multiple autoimmune conditions

Chromosome 6 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Autoimmune, Psoriasis, Inflammation, Rheumatoid Arthritis, Immune & Autoimmune, Anti-TNF Biologics

The TNFAIP3 gene on chromosome 6q23 encodes A20, the immune system's primary brake on NF-κB inflammatory signaling(https://pubmed.ncbi.nlm.nih.gov/32241683/). Multiple independent genetic signals cluster within and around this gene, each perturbing A20-mediated NF-κB suppression through a different mechanism....

rs61750584 Missense variant in the VWF A2 domain that destabilizes the protein and increases ADAMTS13 cleavage, causing loss of high-molecular-weight multimers and von Willebrand disease type 2A with mucocutaneous bleeding

Chromosome 12 Risk Allele G Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Cardiovascular, Genetic Counseling, Carrier Status, Thrombophilia

Von Willebrand factor is the body's primary molecular glue at sites of vascular injury. Synthesized by endothelial cells and platelets, VWF(https://medlineplus.gov/genetics/condition/von-willebrand-disease/) normally circulates as giant multimeric strings. The largest of these high-molecular-weight (HMW) multimers...

rs6841581 Regulatory variant upstream of the endothelin receptor type A gene that reduces EDNRA transcription, impairing endothelin-1-mediated vasoconstriction and increasing susceptibility to intracranial aneurysm

Chromosome 4 Risk Allele A Category Blood Pressure & Hypertension Tags Cerebrovascular, Cardiovascular, Blood Pressure, Endothelial Health, Angiogenesis, Brain Health

The endothelin system is one of the most potent regulators of vascular tone in the human body. Endothelin-1 (ET-1) acts through two receptor subtypes — EDNRA (type A) and EDNRB (type B) — to orchestrate vasoconstriction, vascular smooth muscle proliferation, and arterial wall remodeling. EDNRA is the dominant...

rs7151526 Regulatory variant downstream of SERPINA1 associated with increased susceptibility to ANCA-associated vasculitis (GPA/MPA) and higher mortality in AAV patients

Chromosome 14 Risk Allele A Category B-Cell Immunity & Antibody-Mediated Disease Tags Protease Inhibitor, Autoimmune, Inflammation, Kidney Disease, Lung Health

Alpha-1 antitrypsin (AAT), encoded by SERPINA1, is the body's most abundant serine protease inhibitor and serves as the primary natural inhibitor of Proteinase 3 (PR3)(https://pubmed.ncbi.nlm.nih.gov/23604680/). When AAT function is compromised, unbound PR3 accumulates on neutrophil surfaces and in the circulation,...

rs72551348 Rare pathogenic missense variant in the UGT1A1 gene that severely reduces bilirubin glucuronidation; homozygotes develop Crigler-Najjar syndrome type II with persistent unconjugated hyperbilirubinemia that responds to phenobarbital treatment

Chromosome 2 Risk Allele G Category Uric Acid & Kidney Function Tags Bilirubin, Liver Health, Pharmacogenomics, Drug Metabolism, Carrier Status, Congenital

Every day your liver handles a continuous stream of spent red blood cells, converting their released haemoglobin into bilirubin and then rendering that bilirubin water-soluble so it can be excreted in bile. The enzyme that carries out this final conjugation step is...

rs727428 Regulatory variant 1 kb downstream of the SHBG gene that reduces sex hormone-binding globulin levels; the T allele lowers SHBG by ~10–20%, increasing free testosterone and free estradiol bioavailability and elevating risk for PCOS and androgen-driven metabolic dysfunction.

Chromosome 17 Risk Allele T Category Reproductive Hormones Tags Steroid Hormones, Hormones, Testosterone, PCOS, Fertility, Metabolic Syndrome

Sex hormone-binding globulin is the liver's primary traffic controller for testosterone and estradiol. Only about 1–3% of testosterone circulates as "free" bioactive hormone — the rest is bound to SHBG (roughly 44%) or albumin (54%). When SHBG levels rise, more testosterone gets locked away; when SHBG levels fall,...

rs730882105 Rare LDLR missense variant (c.1570G>A, p.Val524Met) associated with familial hypercholesterolemia; classified as likely pathogenic by the British Heart Foundation LDLR-LOVD registry

Chromosome 19 Risk Allele A Category Atherogenic Lipoproteins Tags Cholesterol, LDL Cholesterol, Cardiovascular, Atherosclerosis, Heart Disease, Statins

The LDL receptor (LDLR) encoded by the LDLR gene is the primary mechanism by which the liver clears low-density lipoprotein (LDL) cholesterol from the bloodstream. Each functional LDLR molecule captures LDL particles at the hepatocyte surface and draws them into the cell via receptor-mediated endocytosis, where...

rs804279 Intergenic variant at the GATA4/NEIL2 locus on chromosome 8p23.1 associated with polycystic ovary syndrome susceptibility; the T allele tags regulatory variation linked to elevated androstenedione and PCOS risk (OR ~1.14), with the strongest effect in NIH-diagnosed PCOS

Chromosome 8 Risk Allele T Category Fertility & Ovarian Function Tags PCOS, Fertility, Hormones, Reproductive Health, Steroid Hormones, Base Excision Repair

On the short arm of chromosome 8, at position 8p23.1, a compact genomic neighbourhood hosts two functionally distinct genes: GATA4(https://www.ncbi.nlm.nih.gov/gene/2626) and NEIL2(https://www.ncbi.nlm.nih.gov/gene/51738). Between and around them sits rs804279, an intergenic variant that large-scale genome-wide...

rs9268839 Intergenic tag SNP upstream of HLA-DRA; the G allele is the primary GWAS signal for rheumatoid arthritis susceptibility in the HLA class II region, with among the strongest effect sizes of any common RA variant (OR ~2.47 in Europeans).

Chromosome 6 Risk Allele G Category Interferon Signaling & Systemic Autoimmune Tags HLA, Rheumatoid Arthritis, Autoimmune, Inflammation, MHC Antigen Presentation, Immune & Autoimmune

The region just upstream of HLA-DRA on chromosome 6p21.32 is home to one of the most powerful common genetic risk signals for rheumatoid arthritis (RA) in the human genome. rs9268839 is an intergenic variant located approximately 16 kilobases upstream of HLA-DRA(https://www.ncbi.nlm.nih.gov/gene/3122), within a...

rs13424006 Intronic IL1RL1 variant in the 10th intron of the ST2 receptor gene; C allele is protective against late-onset wheeze and eosinophilic airway inflammation, reducing risk by approximately 26% per C allele copy in European birth cohorts

Chromosome 2 Risk Allele T Category Allergy & Atopic Disease Tags Asthma, Inflammation, Immune System, Lung Health, Immune & Autoimmune

The IL1RL1 gene(https://pubmed.ncbi.nlm.nih.gov/29083406/) is one of the most replicated loci in allergy and asthma genetics. Most research focuses on variants that increase risk. rs13424006 is notable for the opposite reason: the C allele at this intronic position is protective — carriers have a measurably lower...