Research — GeneOps

rs8192678 Master mitochondrial biogenesis regulator — Ser482 variant reduces PGC-1alpha transcriptional activity, impairing mitochondrial production, aerobic capacity, and metabolic adaptation

Chromosome 4 Risk Allele T Category Fitness & Body Tags Fitness, Endurance, Diabetes, Cardiovascular, Mitochondria, Longevity, Aerobic Capacity, Fat Metabolism, Insulin Resistance

PGC-1alpha (encoded by PPARGC1A) is the master regulator of mitochondrial biogenesis — the cellular process that builds new mitochondria and determines how efficiently your cells produce energy. Every time you exercise, fast, or face cold exposure, PGC-1alpha activates a cascade that grows your mitochondrial...

rs20541 Missense variant in IL-13 that enhances Th2 cytokine signaling, elevating serum IgE and increasing risk for atopic dermatitis, allergic rhinitis, and eczema; the minor A allele (Q130) confers risk while the common G allele (R130) is protective for atopic disease

Chromosome 5 Risk Allele A Category Allergy & Atopic Disease Tags Asthma, Inflammation, Autoimmune, Skin Health, Biologic Therapy, T-Cell Regulation

Interleukin-13 is the central cytokine of type 2 immune responses(https://pubmed.ncbi.nlm.nih.gov/31230370/). While IL-4 drives central T-cell differentiation, IL-13 executes the peripheral tissue damage that defines atopic dermatitis: it remodels the skin barrier, recruits eosinophils, stimulates IgE production,...

rs2236224 Intronic tag variant in MTHFD1 in strong LD with the R653Q missense variant, affecting folate-dependent purine synthesis and maternal neural tube defect risk

Chromosome 14 Risk Allele A Category Methylation & Detox Tags Methylation, Folate, B Vitamins, Homocysteine, Cardiovascular

MTHFD1 (methylenetetrahydrofolate dehydrogenase 1) is a remarkable trifunctional enzyme: a single polypeptide that catalyzes three sequential reactions converting folate derivatives along a one-carbon relay chain. Its three enzyme domains — dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase() —...

rs2471738 Intronic MAPT variant whose T allele co-defines the H1c sub-haplotype, independently conferring OR 1.85 for progressive supranuclear palsy and OR 2.07 for corticobasal degeneration in the same meta-analysis validating rs242557

Chromosome 17 Risk Allele T Category Neurology & Cognition Tags Neurological Risk, Parkinson's, Dementia, Tau Pathology, Brain Health, Aging

The rs2471738 variant is an intronic SNP in the MAPT gene whose T allele is one of six markers that together define the H1c sub-haplotype — the highest-risk configuration within the broad H1 clade of the MAPT locus. While rs242557 is the most widely studied H1c tagging SNP, rs2471738 was independently analyzed in...

rs28399433 Promoter variant that reduces CYP2A6 expression by ~50%, slowing nicotine metabolism and altering response to several cancer and antiretroviral drugs

Chromosome 19 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Smoking, Smoking Related, Cancer Treatment, Carcinogen Metabolism

CYP2A6 is the liver enzyme responsible for metabolizing roughly 70–80% of inhaled nicotine, converting it to its primary inactive metabolite cotinine, and then onward to 3-hydroxycotinine. The rate at which someone clears nicotine from their blood is one of the strongest determinants of how much they smoke and...

rs3487348 Intronic PTPN1 variant in the 100-kb haplotype block; T allele associated with more favorable cholesterol profile (lower total and LDL cholesterol) in lean individuals

Chromosome 20 Risk Allele G Category Blood Sugar & Diabetes Tags Diabetes, Insulin Resistance, Cholesterol, LDL Cholesterol, Metabolic, Cardiovascular

Protein tyrosine phosphatase 1B (PTP1B), encoded by the PTPN1 gene on chromosome 20q13, acts as a molecular brake on insulin signaling. When the insulin receptor is activated, it phosphorylates itself on key tyrosine residues to initiate a signaling cascade that drives glucose uptake and metabolic regulation. PTP1B...

rs3754048 Regulatory variant 2 kb upstream of APH1A where the C allele (paper's G, coding strand) increases YY1 transcription factor binding and drives ~2.7-fold higher APH1A transcription, elevating gamma-secretase activity, increasing Aβ42 production, and raising Alzheimer's disease risk.

Chromosome 1 Risk Allele C Category Hormones & Sleep Tags Alzheimer's, Neurodegeneration, Amyloidosis, Sleep, Circadian, Brain Health

A regulatory variant 2 kb upstream of APH1A sits at the molecular origin of amyloid precursor protein (APP) cleavage. APH1A(https://pubmed.ncbi.nlm.nih.gov/21443683/) is an obligate structural component of the enzyme that cuts APP into fragments, including the neurotoxic Aβ42 peptide — the primary driver of amyloid...

rs3834458 A 3-bp deletion in intron 3 of FADS2 that reduces delta-6 desaturase activity, impairing conversion of the omega-3 precursor ALA to EPA and GLA to arachidonic acid; deletion carriers accumulate ALA in blood while producing less EPA, DPA, and DHA, with effects confirmed in a meta-analysis of 7 trials.

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

In the omega-3 synthesis pathway, alpha-linolenic acid (ALA) from flaxseed and walnuts must pass through a series of enzymatic steps before becoming EPA and DHA — the forms that actively protect the cardiovascular system and brain. The very first step is catalyzed by delta-6...

rs4684854 Intergenic regulatory variant downstream of PPARG associated with central obesity and fat distribution in GWAS analyses; shows markedly different allele frequencies across ancestry groups

Chromosome 3 Risk Allele C Category Fat Storage & Energy Tags Adipogenesis, Fat Distribution, Metabolic Health, Insulin Resistance, Obesity, Cardiovascular

PPARγ(https://pubmed.ncbi.nlm.nih.gov/12663460/) is one of the most consequential metabolic genes in the human body. It governs whether pre-adipocytes become mature fat cells, how adipose tissue distributes between visceral and subcutaneous depots, and how sensitive peripheral tissues remain to insulin. The gene...

rs659366 Promoter variant at position -866 of UCP2 that controls mitochondrial uncoupling protein expression; the T allele (A in coding-strand notation) increases UCP2 transcription, lowering ROS production and reducing insulin resistance, while C-allele homozygotes have lower UCP2 activity and carry higher oxidative-stress burden

Chromosome 11 Risk Allele C Category Longevity & Aging Tags Longevity, Aging, Mitochondria, Oxidative Stress, Cardiovascular, Insulin Resistance

Every cell in your body runs a thermodynamic negotiation: burn fuel to make ATP for biological work, or dissipate that energy as heat through uncoupling(https://pubmed.ncbi.nlm.nih.gov/27364833/). UCP2 — uncoupling protein 2 — sits at the heart of this trade-off. It is expressed widely: in skeletal muscle, immune...