Research — GeneOps

rs11571833 Moderate-penetrance stop-gain variant truncating the last 93 amino acids of BRCA2, associated with modestly increased risk of breast, ovarian, and lung cancers — distinct from pathogenic BRCA2 mutations

Chromosome 13 Risk Allele T Category Cancer Risk Tags Cancer Risk, BRCA, DNA Repair, Cancer Screening, Breast Cancer

BRCA2 is one of the most important DNA repair genes in the human genome, encoding a 3,418-amino acid protein that orchestrates homologous recombination() repair of double-strand DNA breaks. Pathogenic mutations that severely disrupt BRCA2 function carry lifetime breast cancer risks of 45-70% and ovarian cancer risks...

rs10038916 Intronic variant in the AMPA glutamate receptor gene GRIA1 associated with restless legs syndrome risk via hyperglutamatergic thalamic excitability

Chromosome 5 Risk Allele G Category Neurology & Cognition Tags Neurotransmitters, Sleep, Arousal, Neurological Risk, Brain Health, Sensory Processing

Deep inside your brain, the thalamus acts as a sensory relay station — filtering and routing signals between your body and cortex throughout the day, and shifting into a dampened state that allows sleep at night. In restless legs syndrome (RLS), this relay appears to malfunction: something keeps it overstimulated at...

rs10050860 Missense variant (Asp575Asn) in the ERAP1 catalytic domain that modestly reduces peptide trimming efficiency; the protective T allele (Asn575) is co-protective with rs30187 Arg528, with combined homozygous protective state conferring 3-4x lower ankylosing spondylitis risk in HLA-B27-positive individuals

Chromosome 5 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Immune System, Autoimmune, MHC Antigen Presentation, Inflammation, Arthritis, Psoriasis

Your immune system runs a continuous quality-control operation inside every cell. Proteins are constantly degraded, and small fragments — peptides — are trimmed to the correct 8-10 amino acid length(https://pubmed.ncbi.nlm.nih.gov/24352655/) by ERAP1 (Endoplasmic Reticulum Aminopeptidase 1) before being loaded onto...

rs10156191 DAO structural variant affecting enzyme activity and histamine degradation

Chromosome 7 Risk Allele T Category Methylation & Detox Tags Histamine, Food Sensitivity, Detoxification

While rs2052129 affects how much DAO enzyme your body makes, the Thr16Met | Threonine to methionine at position 16 variant (rs10156191) changes the actual structure of the enzyme protein. This is a missense mutation | A missense mutation changes one amino acid to another in the resulting protein that substitutes...

rs10167914 A regulatory tag SNP in the IL1A/IL1B locus on chromosome 2q13; the G allele increases endometriosis risk (OR 1.12) and correlates with elevated IL-1 alpha expression, driving peritoneal inflammation and ectopic lesion establishment.

Chromosome 2 Risk Allele G Category Endometriosis & Uterine Health Tags Endometriosis, Inflammation, Fertility, Reproductive Health, Women's Health, Chronic Pain

Endometriosis — where endometrial-like tissue grows outside the uterus — affects an estimated 10% of reproductive-age women and is driven as much by immune dysfunction as by hormonal disruption. This variant sits within a dense inflammatory gene cluster on chromosome 2q13 that encodes six members of the...

rs10177833 Intronic variant in the sodium bicarbonate cotransporter gene strongly associated with salt-sensitive blood pressure through enhanced renal sodium reabsorption

Chromosome 2 Risk Allele A Category Blood Pressure & Hypertension Tags Blood Pressure, Hypertension, Salt Sensitivity, Kidney Function, Cardiovascular, Renal Function

The connection between salt and blood pressure is not the same for everyone. For about a quarter of the population, sodium intake triggers a pronounced rise in blood pressure — what researchers call salt sensitivity(https://pubmed.ncbi.nlm.nih.gov/22987918/). The SLC4A5 gene — encoding NBCe2, the sodium bicarbonate...

rs10195252 Intergenic variant between GRB14 and COBLL1 that acts as an eQTL for GRB14 in adipose tissue, shifting body fat toward peripheral (hip and limb) versus central (visceral) deposition

Chromosome 2 Risk Allele C Category Blood Sugar & Diabetes Tags Fat Metabolism, Insulin, Lipedema, Fat Distribution, Cardiovascular, Women's Health, Diabetes

Where your body stores fat matters as much as how much fat you carry. Two people with identical BMI can have entirely different metabolic risk profiles depending on whether their excess fat accumulates around their organs (visceral) or in their hips, thighs, and legs (peripheral). The rs10195252 variant in the...

rs10208293 Intronic IL1RL1 variant tagging an independent regulatory signal at the ST2 locus; A allele increases late-onset wheeze risk and affects sST2 (decoy receptor) expression independently of the primary rs1420101 signal

Chromosome 2 Risk Allele A Category Allergy & Atopic Disease Tags Asthma, Inflammation, Immune System, Lung Health, Immune & Autoimmune

The IL1RL1 gene(https://pubmed.ncbi.nlm.nih.gov/29083406/) is home to one of the most replicated loci in allergy genetics. Most people who have heard of ST2 genetics know about rs1420101 — the primary GWAS signal, located roughly 8.6 kilobases away on the same gene. But rs10208293 is something different: a second,...

rs10305492 Rare protective missense variant in the GLP-1 receptor associated with lower fasting glucose, reduced T2D risk, and coronary heart disease protection

Chromosome 6 Risk Allele A Category Pharmacogenomics Tags Drug Metabolism, Diabetes, Insulin, Cardiovascular, Pharmacogenomics

Among the thousands of genetic variants linked to type 2 diabetes, very few are genuinely protective. The rs10305492 variant in the GLP-1 receptor gene(https://www.genecards.org/cgi-bin/carddisp.pl?gene=GLP1R) is one of them. This low-frequency missense variant (about 1.6% allele frequency in Europeans, rare or...

rs1041981 Missense variant in lymphotoxin-alpha, a TNF superfamily cytokine essential for secondary lymphoid organ formation and innate immune coordination; the A allele (Asn at position 26 of mature protein) alters LTα trimer stability, modestly increases cancer susceptibility, and has been associated with coronary atherosclerosis and respiratory infection risk

Chromosome 6 Risk Allele A Category Innate Immunity & Infection Defense Tags Innate Immunity, Inflammation, Infection Risk, Cardiovascular, Cancer Risk, Immune Function

Lymphotoxin-alpha (LTα)(https://www.ncbi.nlm.nih.gov/gene/4049) is one of the founding members of the immune signaling family that includes TNF itself. Unlike TNF, which is broadly expressed by macrophages and adipocytes, LTα is produced predominantly by lymphocytes and has a distinct but overlapping set of...