Research — GeneOps

rs578776 CHRNA3 3' UTR variant at 15q25.1 Locus 2 — mechanistically distinct from rs1051730, associated with blunted reward sensitivity to natural stimuli and heightened neural response to cigarette cues

Chromosome 15 Risk Allele G Category Mood & Behavior Tags Mental Health, Addiction, Smoking, Neurotransmitters, Dopamine

The 15q25.1 chromosomal region harbors two genetically independent signals for nicotine dependence and heavy smoking. The first — rs16969968 in CHRNA5 — encodes a receptor that blunts aversive responses to nicotine, lowering the natural ceiling on how much a person smokes. The second, rs578776, tells a different...

rs61754002 Nonsense mutation creating a premature stop codon in von Willebrand factor; null allele associated with von Willebrand disease

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

Von Willebrand factor (VWF) is a large multimeric glycoprotein that performs two essential roles in hemostasis: it anchors platelets to sites of vascular injury, and it acts as a carrier protein that protects coagulation factor VIII (FVIII) from premature degradation in the bloodstream. When a vessel is damaged, VWF...

rs6548238 Second strongest obesity GWAS locus after FTO - influences hypothalamic appetite regulation

Chromosome 2 Risk Allele C Category Appetite & Obesity Tags Obesity, Appetite, Fat Metabolism, Diabetes, Insulin Resistance

TMEM18 (Transmembrane Protein 18) sits at the second strongest obesity locus ever discovered by genome-wide association studies, trailing only FTO. The variant rs6548238 lies 23 kilobases upstream of TMEM18 on chromosome 2p25.3, in a regulatory region that influences how much TMEM18 protein the brain produces. What...

rs66791338 Intronic 5-bp indel (AAAGG) in the IVD regulatory region that is the primary functional variant controlling IVD expression; the derived deletion allele drives higher enzyme activity and lower isovalerylcarnitine, and is enriched in East Asian populations under positive selection

Chromosome 15 Risk Allele I Category Metabolic Enzymes & Rare Disorders Tags Energy Metabolism, Mitochondria, B Vitamins, Micronutrients, Lung Health, Fibrosis

Every gram of dietary leucine — the most anabolic amino acid, abundant in meat, dairy, and protein powders — is funnelled through a five-step mitochondrial enzymatic cascade before it can be burned for energy or converted to acetyl-CoA. The third and rate-limiting step belongs to isovaleryl-CoA dehydrogenase...

rs6693831 Intronic IL23R variant where the minor T allele is associated with increased ankylosing spondylitis susceptibility and the common C allele confers protection across several IL-23/Th17-driven inflammatory diseases in Asian populations

Chromosome 1 Risk Allele T Category IBD & Mucosal Immunity Tags Autoimmune, Inflammation, Arthritis, IBD, Inflammatory Bowel Disease, Immune & Autoimmune

The interleukin-23 receptor (IL-23R) sits at the center of the IL-23/Th17 axis(https://pubmed.ncbi.nlm.nih.gov/27043356/), one of the most therapeutically targeted pathways in modern inflammatory disease. When IL-23 binds its receptor on CD4+ T cells, innate lymphoid cells, and natural killer cells, it drives...

rs73625113 An intronic regulatory variant in ESR1 at the 6q25.1 locus identified as a high-confidence causal endometriosis SNP (posterior inclusion probability 0.506) through fine-mapping of the Rahmioglu et al. 2023 mega-GWAS; the T allele lies in strong LD with eQTLs driving ESR1 expression and DNA methylation near ESR1, implicating altered estrogen receptor signaling in endometriosis susceptibility and pain subphenotypes including dysmenorrhea and dyspareunia

Chromosome 6 Risk Allele T Category Endometriosis & Uterine Health Tags Endometriosis, Estrogen, Estrogen Metabolism, Women's Health, Pain Management, Reproductive Health

The ESR1 gene encodes estrogen receptor alpha (ERα)(https://pubmed.ncbi.nlm.nih.gov/28537267/), the most pharmacologically targeted protein in endometriosis management. Endometriosis affects roughly 1 in 10 women of reproductive age — causing pelvic pain, dysmenorrhea, dyspareunia, and infertility — and estrogen is...

rs763780 Missense variant that reduces IL-17F bioactivity and acts as a natural IL-17F antagonist, protecting against Th17-driven autoimmune conditions while impairing antifungal mucosal defense

Chromosome 6 Risk Allele C Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Immune Defense, Immune & Autoimmune, Bacterial Clearance, Infection Risk

Interleukin-17F (IL-17F)(https://www.ncbi.nlm.nih.gov/gene/112744) is one of the signature outputs of Th17 cells — the immune subset central to defense against extracellular bacteria and fungi and, when dysregulated, to the tissue damage seen in autoimmune conditions like psoriasis, ankylosing spondylitis, and...

rs17293632 Intronic regulatory variant in SMAD3 that alters TGF-beta effector signaling in regulatory T cells, conferring pleiotropic risk for both allergic disease (asthma, hay fever, eczema) and Crohn's disease through impaired immune tolerance

Chromosome 15 Risk Allele T Category Allergy & Atopic Disease Tags Autoimmune, T-Cell Regulation, Asthma, Crohn's Disease, Gut Health, Inflammation

SMAD3 is the central intracellular messenger of TGF-beta (transforming growth factor-beta) signaling(https://pubmed.ncbi.nlm.nih.gov/29083406/), the master pathway governing immune tolerance and the differentiation of regulatory T cells (Tregs). In the immune system, Tregs depend on TGF-beta–SMAD3 signaling both to...

rs17857135 Missense variant (Met270Thr) in RNF213, the major moyamoya disease susceptibility gene; the C allele reached genome-wide significance for migraine risk (OR=1.06), linking vascular remodeling genetics to common headache disorders

Chromosome 17 Risk Allele C Category Neurology & Cognition Tags Migraine, Neurological Risk, Brain Health, Cardiovascular, Angiogenesis, Cerebrovascular

The RNF213 gene encodes a massive 591-kilodalton protein that sits at the intersection of vascular biology and immune function. Best known as the primary genetic determinant of moyamoya disease(https://pubmed.ncbi.nlm.nih.gov/35605621/), RNF213 variants have now been linked to the much more common condition of...

rs1801131 Second MTHFR variant affecting enzyme activity in the regulatory domain

Chromosome 1 Risk Allele G Category Methylation & Detox Tags Methylation, Folate, B Vitamins, Homocysteine, Thrombophilia

The A1298C variant (rs1801131) is the second most-studied MTHFR variant. While C677T gets most of the attention, A1298C also affects MTHFR enzyme activity, though through a different mechanism and with a milder effect. The Mechanism The A1298C variant causes a glutamic acid-to-alanine substitution | Glutamic...