Research — GeneOps

rs6454674 Intronic variant in the cannabinoid receptor 1 gene that modulates substance dependence vulnerability through a gene-gene interaction with rs806368; the G allele increases risk for drug and alcohol dependence and sits in a completely independent LD block from the rs806368/rs1049353 haplotype

Chromosome 6 Risk Allele G Category Mood & Behavior Tags Addiction, Endocannabinoid, Neurotransmitters, Brain Health, Dopamine, Cannabis

The CNR1 gene encodes CB1(), the master regulator of endocannabinoid signaling across the brain's reward and emotion circuits. Two CNR1 variants — rs806368 and rs1049353 — are already well characterized as a tight haplotype block that modulates CB1 receptor expression and shapes vulnerability to cannabis-related...

rs6922269 Intronic variant in the mitochondrial folate enzyme MTHFD1L, associated with increased coronary artery disease risk and post-ACS cardiovascular mortality through impaired one-carbon unit supply

Chromosome 6 Risk Allele A Category Coronary Artery Disease & Atherosclerosis Tags Cardiovascular, Heart Disease, Folate, B Vitamins, Homocysteine, Methylation

Most people associate folate metabolism with the MTHFR enzyme in the cytoplasm. But folate cycling actually begins in the mitochondria, and a second enzyme — MTHFD1L, the mitochondrial C1-tetrahydrofolate synthase (https://pubmed.ncbi.nlm.nih.gov/19948730/) — does much of the critical upstream work. rs6922269 is an...

rs705379 Promoter polymorphism that controls PON1 gene expression — the T allele (A on the plus strand) reduces transcription factor binding, halving arylesterase activity and lowering HDL-mediated antioxidant protection against LDL oxidation.

Chromosome 7 Risk Allele A Category Vascular Inflammation & Remodeling Tags Cardiovascular, HDL Cholesterol, Oxidative Stress, Antioxidants, Atherosclerosis, Liver Health

Paraoxonase-1 (PON1) is an enzyme that travels on HDL particles(https://pubmed.ncbi.nlm.nih.gov/36118876/) and functions as your bloodstream's primary defense against oxidized LDL — the form of "bad cholesterol" that initiates plaque buildup in artery walls. While most research on PON1 focuses on the coding-region...

rs7530511 Missense variant in the IL-23 receptor that substitutes leucine for proline at position 310; the rare leucine allele (T) is associated with susceptibility to Graves' disease and rheumatoid arthritis through altered IL-23/Th17 immune signaling

Chromosome 1 Risk Allele T Category IBD & Mucosal Immunity Tags Autoimmune, Autoimmunity, Thyroid, Inflammation, Immune System, Immune & Autoimmune

The interleukin-23 receptor (IL-23R(https://www.ncbi.nlm.nih.gov/gene/149233)) sits at a pivotal junction in the immune system: it receives signals from IL-23, a cytokine produced by dendritic cells and macrophages, and translates them into activation of Th17 cells(https://en.wikipedia.org/wiki/Thelper17cell)....

rs7566605 Upstream regulatory variant near INSIG2 that influences lipogenesis control and has been associated with BMI, subcutaneous fat accumulation, and obesity risk in multiple populations

Chromosome 2 Risk Allele C Category Appetite & Obesity Tags Obesity, Fat Metabolism, Diet, Cholesterol, Insulin, Cardiovascular

Every time you eat, your body must decide how much cholesterol and fat to synthesize versus burn. That decision runs through a molecular checkpoint in the endoplasmic reticulum controlled by a family of proteins called Insigs. INSIG2 — insulin-induced gene 2 — is a membrane sensor that binds...

rs80338701 Second most common pathogenic PMM2 allele (p.Phe119Leu); in compound heterozygosity with R141H produces the classic PMM2-CDG phenotype with cerebellar hypoplasia, intellectual disability, and multi-organ glycosylation failure; homozygosity is likely lethal

Chromosome 16 Risk Allele A Category Metabolic Enzymes & Rare Disorders Tags Congenital, Carrier Status, Genetic Counseling, Metabolic, Neurological Risk, Micronutrients

Every protein passing through the secretory pathway must be N-glycosylated() before it can fold correctly and exit the cell. The enzyme phosphomannomutase 2 (PMM2) is indispensable for this process: it converts mannose-6-phosphate to mannose-1-phosphate, the precursor that feeds into GDP-mannose and ultimately into...

rs9383935 3' UTR variant in CCDC170 at the 6q25.1 estrogen-signaling locus; the T allele disrupts a miR-27a binding site, reducing CCDC170 expression and increasing breast cancer risk (OR 1.38 in Chinese women); the same locus independently confers endometriosis susceptibility

Chromosome 6 Risk Allele T Category Endometriosis & Uterine Health Tags Endometriosis, Estrogen, Breast Cancer, Cancer Risk, Women's Health, Reproductive Health

At chromosome 6q25.1, the estrogen receptor alpha gene ESR1 sits next to CCDC170 (Coiled-Coil Domain Containing 170), a gene whose protein organizes the Golgi apparatus and its microtubule connections inside cells. This locus is one of the most intensively studied regions in cancer and reproductive genetics — it has...

rs1802059 Synonymous MTRR variant (c.1911G>A) associated with congenital heart disease risk in offspring and maternal carriers, likely through regulatory effects on B12 recycling capacity

Chromosome 5 Risk Allele A Category Methylation & Detox Tags Methylation, B Vitamins, Homocysteine, Cardiovascular, Folate

The MTRR gene (methionine synthase reductase) encodes the enzyme responsible for keeping methionine synthase (MTR) operational. MTR converts homocysteine to methionine using methylcobalamin | The methyl-carrying, active form of vitamin B12 (active B12) as a cofactor, but during each catalytic cycle B12 becomes...

rs1805010 Missense variant in the extracellular domain of the IL-4 receptor alpha chain that increases IL-4 signaling sensitivity; the Val75 (G) allele is found in 80% of allergic bronchopulmonary aspergillosis patients and elevates IgE-driven Th2 immune responses in asthma and atopic disease

Chromosome 16 Risk Allele G Category Allergy & Atopic Disease Tags Asthma, Immune Response, Inflammation, JAK-STAT Signaling, Biologic Therapy, Lung Health

Interleukin-4(https://pubmed.ncbi.nlm.nih.gov/30408936/) acts through a dimeric receptor on the surface of immune cells. The alpha chain of this receptor (IL-4Rα, encoded by IL4R on chromosome 16) is the critical ligand-binding component shared by both the type I receptor (IL-4Rα + γc, on lymphocytes) and the type...

rs193922916 Recessive pathogenic APP missense variant causing early-onset Alzheimer's disease in homozygotes; heterozygous carriers are unaffected due to a dominant-negative inhibition of amyloid aggregation

Chromosome 21 Risk Allele A Category Neurology & Cognition Tags Alzheimer's, Neurodegeneration, Cognitive Decline, Amyloidosis, Carrier Status, Genetic Counseling

The amyloid precursor protein (APP) gene encodes a large transmembrane protein whose sequential cleavage by beta-secretase (BACE1)(https://pubmed.ncbi.nlm.nih.gov/28626014/) and gamma-secretase generates the amyloid-beta (Aβ) peptides central to Alzheimer's disease pathology. Most pathogenic APP mutations cluster...