Research — GeneOps

rs17219084 FTO intron variant in the extended obesity-associated region, with exploratory association with Alzheimer's disease risk through metabolic pathways

Chromosome 16 Risk Allele G Category Fitness & Body Tags Obesity, Metabolic, Fat Metabolism, Appetite, Exercise, Diet

The FTO (fat mass and obesity-associated) gene(https://pubmed.ncbi.nlm.nih.gov/17434869/) sits at the strongest and most replicated genetic locus for common human obesity. The best-studied variants cluster in a 47-kilobase block spanning the first two introns, where regulatory changes shift adipocyte biology toward...

rs174548 Intronic regulatory variant in FADS1 that reduces delta-5 desaturase expression, impairing conversion of linoleic acid to arachidonic acid and ALA to EPA — one of the strongest GWAS hits for plasma PUFA levels.

Chromosome 11 Risk Allele G Category Triglycerides & Fatty Acids Tags Omega-3, Fat Metabolism, Cardiovascular, Diet, Vitamins, Micronutrients

Your ability to build the long-chain omega-3s that your brain, heart, and immune system rely on is not just about what you eat — it depends on how efficiently your body can convert short-chain fatty acids into their active forms. FADS1 encodes delta-5 desaturase(), the enzyme that sits at the critical bottleneck...

rs17576 Missense variant in the MMP9 fibronectin type II domain affecting matrix metalloproteinase-9 substrate binding; the A allele (Gln279) is associated with altered plaque remodeling dynamics, increased intracranial atherosclerotic stenosis risk, and higher ischemic stroke susceptibility compared with the Arg279 (G allele) form

Chromosome 20 Risk Allele A Category Coronary Artery Disease & Atherosclerosis Tags Atherosclerosis, Cardiovascular, Extracellular Matrix, Inflammation, Cerebrovascular, Heart Disease

Your arteries are not static pipes. Their walls constantly remodel — a process driven in large part by matrix metalloproteinase-9 (MMP-9), an enzyme that dissolves the protein scaffolding holding arterial tissue together. When MMP-9 is active in the wrong place at the wrong time, it weakens the fibrous cap...

rs17697419 Intronic variant in the primary lymphangiogenesis growth factor gene; the minor A allele is protective against diabetic retinopathy and diabetic macular edema, reducing risk by ~33%

Chromosome 4 Risk Allele G Category Vascular Inflammation & Remodeling Tags Cardiovascular, Diabetes, Inflammation, Retinal Health

Diabetic retinopathy and its most vision-threatening complication, diabetic macular edema(https://pubmed.ncbi.nlm.nih.gov/26072347/), arise from a combination of chronic hyperglycemia, neuroinflammation, and pathological retinal neovascularization. The VEGFC gene(https://omim.org/entry/601528) at chromosome 4q34...

rs1799958 Common missense variant in ACADS encoding short-chain acyl-CoA dehydrogenase; the A allele (Gly209Ser) reduces SCAD enzyme activity and is associated with mildly elevated butyrylcarnitine (C4) on newborn screening, but is classified as benign to likely-benign and is not a cause of clinical SCAD deficiency

Chromosome 12 Risk Allele A Category Metabolic Enzymes & Rare Disorders Tags Fat Metabolism, Mitochondria, Metabolic, Energy Metabolism, Carrier Status

ACADS(https://www.ncbi.nlm.nih.gov/gene/35) encodes short-chain acyl-CoA dehydrogenase (SCAD), which initiates oxidation of the shortest-chain fatty acids produced during the breakdown of branched-chain amino acids and even-chain dietary fats. The G209S variant (c.625GA, p.Gly209Ser) changes glycine to serine at...

rs1800955 Promoter variant that modulates dopamine D4 receptor expression in the prefrontal cortex, influencing novelty seeking and cognitive flexibility

Chromosome 11 Risk Allele C Category Mood & Behavior Tags Cognition, Dopamine, Neurotransmitters, Brain Health, Stress

Deep in the prefrontal cortex — the brain region responsible for planning, decision-making, and impulse control — sits a receptor that helps determine how you respond to novelty, risk, and reward. The dopamine D4 receptor() is encoded by the DRD4 gene, and its promoter variant() rs1800955 (-521CT) determines how...

rs193922239 Pathogenic missense variant in fibrillin-1 replacing glycine 2627 with arginine in a calcium-binding EGF-like domain, disrupting microfibril assembly and predisposing heterozygous carriers to Marfan syndrome with aortic root dilation, lens dislocation, and skeletal overgrowth.

Chromosome 15 Risk Allele G Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Connective Tissue, Genetic Counseling, Carrier Status, Extracellular Matrix

Every arterial wall, every lens zonule, every ligament that holds your skeleton together depends on a microscopic scaffolding called the microfibril(https://www.ncbi.nlm.nih.gov/books/NBK1335/). Fibrillin-1 is encoded by FBN1 — a 66-exon gene on chromosome 15 producing a 2,871-amino-acid glycoprotein studded with 47...

rs1943226 Upstream regulatory tag variant ~3 kb proximal to MC4R, included in MC4R haplotype studies; appears in a large BMI GWAS at p=1×10⁻²⁶ through LD with the MC4R locus, with no independent obesity association established in direct association studies

Chromosome 18 Risk Allele G Category Appetite & Obesity Tags Appetite, Obesity, Metabolic, Satiety, Fat Distribution, Energy Metabolism

The melanocortin-4 receptor (MC4R) gene is the best-characterized monogenic and polygenic obesity locus known. Hypothalamic MC4R neurons sit at the convergence of leptin and melanocortin signaling: when fat stores are adequate, POMC neurons release alpha-MSH, which binds MC4R to suppress appetite and raise energy...

rs2046210 Promoter-region variant upstream of estrogen receptor alpha (ESR1) at 6q25.1; the A allele increases ESR1 transcription and is associated with elevated endometriosis risk, endometrial cancer susceptibility, and breast cancer risk across multiple populations

Chromosome 6 Risk Allele A Category Endometriosis & Uterine Health Tags Endometriosis, Estrogen, Estrogen Metabolism, Reproductive Health, Women's Health, Breast Cancer

Estrogen receptor alpha (ERα), encoded by ESR1, is the master mediator of estrogen's effects on reproductive tissue. It sits in the nucleus of endometrial, breast, and uterine cells, waiting for estrogen to arrive — and when it does, it binds estrogen and turns on hundreds of downstream genes controlling cell...

rs2066844 Missense variant in the NOD2 gene that increases Crohn's disease risk, particularly ileal disease, by impairing bacterial peptidoglycan recognition

Chromosome 16 Risk Allele T Category IBD & Mucosal Immunity Tags Innate Immunity, Gut Microbiome, Inflammatory Bowel Disease, Ileal Health, Bacterial Sensing, Paneth Cells

Your gut hosts trillions of bacteria, and your immune system must constantly distinguish friend from foe. The NOD2 gene encodes an intracellular bacterial sensor(https://pubmed.ncbi.nlm.nih.gov/11385576/) that acts as a pattern-recognition receptor for bacterial peptidoglycans. When functioning normally, NOD2 helps...