Research — GeneOps

rs3798220 Missense variant in the protease-like domain of apolipoprotein(a) causing markedly elevated Lp(a) levels and substantially increased risk of coronary artery disease, peripheral vascular disease, and aortic valve stenosis; carriers show differential benefit from aspirin therapy

Chromosome 6 Risk Allele C Category Atherogenic Lipoproteins Tags Cardiovascular, Cholesterol, Blood Thinners, Aspirin Response

Lipoprotein(a), or Lp(a), is an LDL-like particle distinguished by an additional apolipoprotein(a) protein component(https://omim.org/entry/152200). The rs3798220 variant causes an isoleucine-to-methionine substitution (p.Ile1891Met, also written Ile4399Met in legacy numbering) in the protease-like domain of...

rs1056836 Phase I detoxification enzyme that hydroxylates estradiol to potentially genotoxic 4-hydroxyestradiol and activates environmental procarcinogens including PAHs

Chromosome 2 Risk Allele C Category Methylation & Detox Tags Detoxification, Phase I, Estrogen Metabolism, Cancer Risk, Antioxidants

CYP1B1 is a Phase I cytochrome P450 enzyme() with a dual role that makes it uniquely important in cancer biology. First, it converts estradiol into 4-hydroxyestradiol (4-OH-E2)(), the most genotoxic of the estrogen metabolites. Second, it activates environmental procarcinogens including polycyclic aromatic...

rs10885406 Intronic TCF7L2 variant tagging the diabetes-risk haplotype and associated with elevated proinsulin/insulin ratio through impaired beta-cell insulin processing

Chromosome 10 Risk Allele G Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Insulin Resistance, Metabolic Health, Energy Metabolism

TCF7L2 — Transcription Factor 7-Like 2 — is the strongest common genetic risk locus for type 2 diabetes in populations of European, African, and South Asian descent. The gene encodes a nuclear transcription factor that is a central effector of the Wnt/β-catenin signaling...

rs11136000 Intronic variant in clusterin gene affecting Alzheimer's disease risk through regulation of amyloid-beta clearance

Chromosome 8 Risk Allele C Category Neurology & Cognition Tags Alzheimer's, Neurological Risk, Cardiovascular, Neuroprotection, Inflammation

Clusterin (also known as apolipoprotein J(https://www.ncbi.nlm.nih.gov/gene/1191)) is a neuroprotective chaperone protein that plays a critical role in clearing toxic protein aggregates from the brain. This genetic variant, located deep within the CLU gene on chromosome...

rs1154404 Intronic variant in ADH5 (GSNOR) in near-complete LD (r²=0.99) with adjacent promoter SNPs at a potential NF-κB binding site; the common A allele tags the asthma risk haplotype associated with elevated GSNOR transcription, GSNO depletion, and increased childhood asthma susceptibility, while the protective T allele is associated with reduced GSNOR expression and lower asthma risk

Chromosome 4 Risk Allele A Category Allergy & Atopic Disease Tags Asthma, Nitric Oxide, Lung Health, Inflammation, Environmental Toxins, Oxidative Stress

Every breath you take depends on a delicate balance between molecules that keep bronchial smooth muscle relaxed and inflammatory signals that tighten it. S-nitrosoglutathione (GSNO)(https://pubmed.ncbi.nlm.nih.gov/19395503/) is one of the lung's most powerful endogenous bronchodilators — and its concentration in the...

rs11590235 TGF-beta signaling regulator variant identified as the top shared locus between migraine and type 2 diabetes

Chromosome 1 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Inflammation, Cardiovascular, Diabetes, Insulin Resistance

The SKI proto-oncogene encodes a transcriptional co-repressor that acts as one of the most potent negative regulators of the TGF-beta signaling pathway(). The rs11590235 variant, located within an intron of SKI on chromosome 1p36.33, achieved the highest statistical significance of any shared locus between migraine...

rs116855232 Nucleotide diphosphatase that inactivates toxic thiopurine metabolites; reduced function causes severe myelosuppression at standard drug doses

Chromosome 13 Risk Allele T Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Chemotherapy, Cancer Treatment, Immunosuppressants, Autoimmune, IBD, Crohn's Disease

Thiopurines(https://www.ncbi.nlm.nih.gov/books/NBK100661/) are essential medications but carry a narrow therapeutic window(https://pubmed.ncbi.nlm.nih.gov/26878724/) that makes them dangerous without proper dose adjustment. For decades, pharmacogenetic testing focused exclusively on TPMT (thiopurine...

rs116862713 Rare AMPK beta-1 subunit variant linking central energy sensing to shared migraine and type 2 diabetes susceptibility

Chromosome 12 Risk Allele T Category Fat Storage & Energy Tags Diabetes, Insulin Resistance, Energy Metabolism, Metabolic Health

PRKAB1 encodes the beta-1 regulatory subunit of AMP-activated protein kinase (AMPK)(), the cell's master fuel gauge. AMPK monitors the ratio of AMP to ATP in every cell and triggers metabolic adaptations when energy is scarce: switching on glucose uptake, fatty acid oxidation, and mitochondrial biogenesis while...

rs12086634 Modulates local cortisol activation from cortisone in liver and adipose tissue, influencing visceral fat, insulin sensitivity, and metabolic syndrome risk

Chromosome 1 Risk Allele G Category Hormones & Sleep Tags Cortisol, HPA Axis, Metabolic Syndrome, Insulin Resistance, Fat Metabolism, Bone Health

Your adrenal glands release cortisone, an inactive form of cortisol, into the bloodstream. Inside tissues — particularly liver, adipose tissue, and brain — the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1, encoded by HSD11B1) converts cortisone back into active...

rs121918388 Nonsense variant creating a premature stop codon at amino acid 2279 of apolipoprotein B-100, producing a severely truncated apoB-50 protein and causing familial hypobetalipoproteinemia type 1 with markedly reduced LDL cholesterol and hepatic steatosis risk

Chromosome 2 Risk Allele A Category Cholesterol & Lipoproteins Tags Fat Metabolism, Cholesterol, Cardiovascular, Liver Health, Vitamins, Carrier Status

Apolipoprotein B-100 (ApoB-100)(https://pubmed.ncbi.nlm.nih.gov/1619387/) is the largest secreted protein in the human body. The rs121918388 variant converts codon 2279 of the APOB gene from glutamine (CAG) to a premature stop codon (TAG) on the coding strand — or equivalently, the GA change seen on the GRCh38 plus...