Research — GeneOps

rs1927911 Intronic TLR4 variant in the innate immune receptor gene; the A allele associates with modestly reduced vascular inflammation and lower risk of nonfatal myocardial infarction, while the common GG genotype is linked to higher atherosclerotic cerebral infarction risk

Chromosome 9 Risk Allele G Category Vascular Inflammation & Remodeling Tags Inflammation, Cardiovascular, Innate Immunity, Atherosclerosis, Immune Response, Heart Disease

Atherosclerosis has long been recognized as more than a simple plumbing problem — it is fundamentally an inflammatory disease. At its center sits Toll-Like Receptor 4 (TLR4)(https://www.ncbi.nlm.nih.gov/gene/7099). When TLR4 fires, it triggers NF-κB signaling and a cascade of pro-inflammatory cytokines — TNF-α,...

rs2229765 Synonymous IGF1R variant associated with lower circulating IGF-1 levels and enrichment in long-lived populations — affects mRNA splicing despite preserving the amino acid sequence

Chromosome 15 Risk Allele G Category Longevity & Aging Tags Longevity, Insulin, Growth Factors, Aging, Diet

Of all the genetic pathways linked to longevity, the insulin/IGF-1 signaling (IIS) pathway(https://pubmed.ncbi.nlm.nih.gov/12483226/) is the most replicated. This variant in IGF1R — the gene encoding the insulin-like growth factor 1 receptor — sits at the very hub of that pathway. It is a synonymous variant, meaning...

rs2249891 Intronic ABCA1 variant associated with lower HDL-cholesterol susceptibility and coronary heart disease risk at one of the most replicated lipid GWAS loci

Chromosome 9 Risk Allele G Category Cholesterol & Lipoproteins Tags Cholesterol, Cardiovascular, Fat Metabolism, HDL Cholesterol

Your body cannot manufacture high-density lipoprotein particles from scratch — it has to build them one lipid at a time. The key enzyme driving that process is ABCA1(https://pubmed.ncbi.nlm.nih.gov/16704350/). rs2249891 sits in the fourth intron of the ABCA1 gene and is one of several common variants at this locus...

rs2301436 Intronic variant in FGFR1OP (CEP43) at the RNASET2-FGFR1OP-CCR6 autoimmune susceptibility locus, with the T allele increasing risk for Crohn's disease, rheumatoid arthritis, and related autoimmune conditions

Chromosome 6 Risk Allele T Category IBD & Mucosal Immunity Tags Autoimmune, Crohn's Disease, Inflammatory Bowel Disease, IBD, Immune & Autoimmune, Inflammation

Chromosome 6q27 hosts one of the most consistently replicated autoimmune susceptibility loci in the human genome. The region — spanning RNASET2, FGFR1OP (also called CEP43), and CCR6 — has been independently confirmed in genome-wide association studies for Crohn's disease(https://pubmed.ncbi.nlm.nih.gov/18587394/),...

rs2568958 Intergenic tag SNP near NEGR1 associated with elevated BMI and major depression risk through hypothalamic NEGR1 expression — one of the most replicated obesity GWAS loci and a genome-wide significant depression locus

Chromosome 1 Risk Allele G Category Mood & Behavior Tags Depression, Mood, Appetite, Obesity, Neuroplasticity, Brain Health

Most genetic risk factors influence one thing. NEGR1() influences two. Variants near this gene are among the most replicated findings in both the obesity and the major depression genetics literature — the same neurons that control appetite circuits in the hypothalamus also organize the monoaminergic signaling that...

rs267606898 Heteroplasmic missense variant in the mitochondrially encoded ND5 subunit of complex I, causing variable-penetrance mitochondrial disease including Leigh syndrome, MELAS, and Leber optic atrophy depending on mutation load.

Chromosome MT Risk Allele A Category Metabolic Enzymes & Rare Disorders Tags Mitochondria, Energy Metabolism, Neurodegeneration, Carrier Status, Genetic Counseling, Fatigue

Every cell in your body runs on ATP — the molecular currency of energy — manufactured by the electron transport chain(https://pubmed.ncbi.nlm.nih.gov/15767514/). Complex I (NADH:ubiquinone oxidoreductase) is the first and largest of these complexes, accepting electrons from cellular metabolism and using their energy...

rs3184504 Pleiotropic missense variant reducing SH2B3 inhibitory function, increasing blood pressure, CAD risk, platelet count, and susceptibility to autoimmune diseases

Chromosome 12 Risk Allele T Category Coronary Artery Disease & Atherosclerosis Tags Cardiovascular, Inflammation, Autoimmune, Blood Pressure, Thrombosis, Longevity, Thrombophilia

SH2B3 (also known as LNK) encodes an adaptor protein that acts as a negative regulator of cytokine and growth-factor signalling(https://pubmed.ncbi.nlm.nih.gov/27430239/). The rs3184504 variant swaps arginine for tryptophan at position 262 in the pleckstrin homology domain, partially disabling this brake. The result...

rs33996649 Protective loss-of-function variant in the PTPN22 catalytic domain that reduces phosphatase activity and lowers risk of SLE, RA, and ulcerative colitis

Chromosome 1 Risk Allele T Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Immune System, Lupus, Rheumatoid Arthritis, Inflammatory Bowel Disease, Immune & Autoimmune

The PTPN22 gene encodes lymphoid tyrosine phosphatase (LYP), a master brake on T-cell and B-cell activation. While the well-known R620W variant (rs2476601) increases autoimmune risk by disrupting regulatory interactions, the R263Q variant works through an entirely different mechanism — it reduces the catalytic...

rs371898076 Pathogenic missense variant in the myosin motor domain causing hypertrophic cardiomyopathy with a 47% lifetime atrial fibrillation rate in affected adults; requires family cardiac screening

Chromosome 14 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Genetic Counseling, Carrier Status, Fibrosis

Beta-myosin heavy chain (MYH7) is the molecular engine of the heart. Together with actin filaments, it generates the forceful contraction that drives blood out of the left ventricle with every beat. The Arg663His variant — a substitution of arginine for histidine at position 663 of the protein — sits directly in the...

rs3743930 Exon 2 missense variant in the inflammasome regulator pyrin; the most common and most debated MEFV variant, classified as likely benign by most clinical labs but associated with mild FMF-like symptoms in some homozygous carriers, especially in Middle Eastern and East/South Asian populations

Chromosome 16 Risk Allele G Category TNF, NF-kB & Inflammatory Cytokines Tags Innate Immunity, Inflammation, Autoimmune, Ancestry-Specific, Amyloidosis, Carrier Status

The MEFV gene encodes pyrin(https://www.ncbi.nlm.nih.gov/gene/4210), the two cytokines that drive the spiking fevers and serositis of familial Mediterranean fever (FMF). Most pathogenic MEFV mutations cluster in exon 10 — M694V, M680I, V726A — and produce a structurally destabilized pyrin that cannot properly gate...