Research — GeneOps

rs1801278 Missense variant in insulin receptor substrate 1 that impairs tyrosine phosphorylation and PI3-kinase recruitment, reducing insulin signaling and increasing type 2 diabetes risk and oral antidiabetes drug failure

Chromosome 2 Risk Allele T Category Blood Sugar & Diabetes Tags Insulin Resistance, Diabetes, Insulin, Metabolic, Pancreatic Beta Cell, Energy Metabolism

When insulin lands on your cell surface, it triggers a molecular relay race. The insulin receptor fires first, then immediately hands the baton to IRS1 — insulin receptor substrate 1 — which recruits the PI3-kinase enzyme that drives glucose uptake into your cells. IRS1 is not just a passive relay; it is the...

rs2070676 Intronic CYP2E1 variant tagging the *1B haplotype; C allele marks reduced CYP2E1 expression and is associated with adverse drug reactions during tuberculosis treatment

Chromosome 10 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Liver Health, Alcohol, Ancestry-Specific, Environmental Toxins

CYP2E1 is the liver enzyme at the centre of two important clinical scenarios: it converts a fraction of every acetaminophen dose into NAPQI(https://pubmed.ncbi.nlm.nih.gov/8662637/), and it generates reactive intermediates from isoniazid, the backbone of tuberculosis treatment. rs2070676 is an intronic variant in...

rs2275780 5' UTR variant in the APH1A gamma-secretase subunit gene, located 21 bp upstream of the translation start codon; studied alongside the -980C/G risk variant in sporadic Alzheimer's disease but not independently associated with disease risk

Chromosome 1 Risk Allele T Category Hormones & Sleep Tags Alzheimer's, Brain Health, Notch Signaling, Neurodegeneration, Amyloidosis

The gamma-secretase complex(https://pubmed.ncbi.nlm.nih.gov/17047368/) is assembled from four essential subunits: presenilin (the catalytic core), nicastrin, PEN-2, and APH-1. Of the APH-1 paralogs, APH1A(https://www.ncbi.nlm.nih.gov/gene/51107) is the dominant form — expressed broadly across all tissues, essential...

rs2304795 Synonymous exon 8 variant in perilipin 1 that tags a haplotype associated with fat mobilization efficiency and sex-specific obesity risk

Chromosome 15 Risk Allele G Category Fat Storage & Energy Tags Fat Metabolism, Obesity, Diet, Insulin, Cardiovascular

Perilipin 1 (PLIN1) is the most abundant protein coating lipid droplets(https://pmc.ncbi.nlm.nih.gov/articles/PMC2838643/) in fat cells. Think of it as a bouncer at the door to your fat stores — in the unfed state, perilipin keeps lipases locked out, preventing uncontrolled fat breakdown. When energy is needed and...

rs2727270 Intronic regulatory variant in FADS2 that tags a 10-SNP haplotype reducing basal FADS1 and FADS2 expression, lowering long-chain PUFA synthesis capacity and arachidonic acid levels; T allele carriers have lower D5D and D6D activity and reduced fasting insulin.

Chromosome 11 Risk Allele T Category Triglycerides & Fatty Acids Tags Omega-3, Fat Metabolism, Micronutrients, Cardiovascular, Insulin

Deep in chromosome 11's FADS gene cluster, rs2727270 sits inside the first intron of FADS2 — not in a coding region, but in a regulatory hotspot that acts as a volume control for the entire fatty acid desaturation cascade. The T allele tags a 10-SNP haplotype spanning FADS2 intron 1 that reduces how much of the key...

rs2802292 Longevity-associated intronic enhancer variant with 1.9-fold increased probability of reaching age 95

Chromosome 6 Risk Allele T Category Longevity & Aging Tags Longevity, Aging, Cardiovascular, Diabetes, Oxidative Stress, Inflammation, Ovarian Reserve, Menopause

FOXO3 encodes a transcription factor that sits at the crossroads of aging biology, coordinating cellular responses to stress, nutrient availability, and oxidative damage. Among the hundreds of genetic variants studied for longevity associations, rs2802292 stands alone: carriers of its protective G-allele have a...

rs3025058 Promoter polymorphism affecting MMP3 enzyme expression levels, influencing cartilage degradation and connective tissue remodeling

Chromosome 11 Risk Allele T Category Fitness & Body Tags Bone & Joint, Inflammation, Cardiovascular, Connective Tissue, Aging, Extracellular Matrix

Matrix metalloproteinase-3 (MMP-3), also called stromelysin-1, is one of the body's primary enzymes for breaking down the extracellular matrix — the structural scaffolding that holds tissues together. MMP-3 degrades collagen types II, III, IV, IX, and X, along with proteoglycans, fibronectin, laminin, and...

rs397516923 Rare truncating variant in desmoplakin that creates a premature stop codon at position 72, disrupting cardiac desmosomal integrity and predisposing carriers to arrhythmogenic cardiomyopathy with predominantly left ventricular involvement.

Chromosome 6 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Fibrosis, Carrier Status, Arrhythmia

Desmoplakin is the molecular anchor that holds heart muscle cells together. Encoded by the DSP gene(https://www.ncbi.nlm.nih.gov/gene/1832), it forms the cytoplasmic half of desmosomes(https://pubmed.ncbi.nlm.nih.gov/32372669/). In the heart, where each cell is pulled and squeezed with every beat, intact desmosomes...

rs4729189 Intronic PON2 variant associated with variation in serum paraoxonase activity; the T allele tags a haplotype with reduced PON2-mediated antioxidant protection in vascular cells and macrophages, modestly increasing susceptibility to oxidative stress-driven atherosclerosis

Chromosome 7 Risk Allele T Category Vascular Inflammation & Remodeling Tags Antioxidants, Atherosclerosis, Cardiovascular, Oxidative Stress, Inflammation, Endothelial Health

Deep inside your vascular cells and immune macrophages, a small enzyme called paraoxonase-2 is running continuous oxidative damage control. Unlike its more famous cousin PON1 — which floats through the bloodstream attached to HDL — PON2 is exclusively intracellular(https://pubmed.ncbi.nlm.nih.gov/29255397/),...

rs4783961 CETP promoter variant that raises HDL cholesterol by reducing cholesteryl ester transfer protein activity; A allele carriers show higher HDL-C but mixed cardiovascular outcome evidence.

Chromosome 16 Risk Allele A Category Cholesterol & Lipoproteins Tags Fat Metabolism, Cholesterol, HDL Cholesterol, Cardiovascular, Omega-3

Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that shuttles cholesteryl esters from HDL particles to LDL and VLDL particles in exchange for triglycerides. It is one of the central regulators of HDL cholesterol concentration in the bloodstream. Less CETP activity means fewer cholesteryl esters...