Research — GeneOps

rs6849729 Intronic SLC2A9 variant 70 bp from rs6815001 tagging the same renal urate-clearance haplotype; the T allele is associated with reduced urate excretion and elevated serum uric acid, while the C allele tags the protective haplotype that supports more efficient renal urate clearance

Chromosome 4 Risk Allele T Category Uric Acid & Kidney Function Tags Gout, Uric Acid, Kidney Function, Cardiovascular, Diet

The SLC2A9 gene encodes GLUT9(https://pubmed.ncbi.nlm.nih.gov/18327257/), the largest known genetic determinant of serum uric acid levels in humans. Genetic variants across the SLC2A9 locus account for more of the variance in serum urate than any other single genomic region — more than dietary purines, more than...

rs700519 Coding variant in aromatase that substitutes cysteine for arginine at position 264; in vitro evidence shows increased aromatase activity, with reported associations with PCOS risk and ART pregnancy outcomes in some populations

Chromosome 15 Risk Allele A Category Reproductive Hormones Tags Aromatase, Fertility, Reproductive Health, Estrogen, PCOS, Uterine Fibroids

Aromatase(https://www.ncbi.nlm.nih.gov/gene/1588) is expressed in the ovaries, adipose tissue, placenta, bone, breast, and brain. It is the only enzyme in vertebrates capable of producing estrogens, making it central to reproductive function, bone metabolism, and hormone balance throughout the lifespan. The rs700519...

rs708272 Influences HDL cholesterol levels and particle size through effects on cholesterol ester transfer protein activity

Chromosome 16 Risk Allele G Category Atherogenic Lipoproteins Tags Cardiovascular, Cholesterol, Longevity, Diet, Alcohol

The cholesterol ester transfer protein (CETP) is a liver-synthesized glycoprotein(https://pubmed.ncbi.nlm.nih.gov/36411553/) that orchestrates cholesterol trafficking between lipoprotein particles. CETP transfers cholesteryl esters from HDL (high-density lipoprotein, the "good" cholesterol) to LDL and VLDL...

rs7574865 Intronic STAT4 variant that amplifies the interferon-alpha and IL-12 response, conferring the strongest common genetic risk for lupus outside the HLA region

Chromosome 2 Risk Allele T Category Interferon Signaling & Systemic Autoimmune Tags Immune & Gut, Lupus, Interferon, Autoimmune, Rheumatoid Arthritis, Inflammation

STAT4 (Signal Transducer and Activator of Transcription 4) is a transcription factor at the center of the type I interferon and IL-12 signaling network. When the immune system detects a threat, interferon-alpha and IL-12 bind receptors on T cells(https://pubmed.ncbi.nlm.nih.gov/17804842/), triggering STAT4...

rs7759938 Regulatory variant near LIN28B associated with puberty timing — the T allele is linked to earlier menarche in females and earlier puberty in males, with implications for reproductive window length and age-at-onset of fertility

Chromosome 6 Risk Allele T Category Fertility & Ovarian Function Tags Puberty Timing, Fertility, Reproductive Health, Hormones, Uterine Fibroids

LIN28B encodes an RNA-binding protein that acts as one of the master regulators of developmental timing in humans. Its primary molecular job is to block the maturation of let-7 microRNAs(https://pubmed.ncbi.nlm.nih.gov/19448623/), which in turn keeps the body in a growth-permissive state. When LIN28B activity...

rs13408661 Intronic variant in IL1RL1 (encoding the ST2 receptor for IL-33) tagging haplotypes associated with lower soluble ST2 (sST2) levels; reduced sST2 decoy activity allows more unchecked IL-33 signaling, increasing type 2 inflammatory tone and susceptibility to asthma

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

IL1RL1(https://pubmed.ncbi.nlm.nih.gov/27699235/) occupies a pivotal position in type 2 immunity: it controls how vigorously the immune system responds to allergens, parasites, and airway insults. The gene on chromosome 2q12.1 produces two functionally distinct proteins. The membrane-anchored form, ST2L, sits on the...

rs145999145 Rare missense variant in the lysosomal exonuclease PLD3 that impairs endolysosomal function and amyloid precursor protein processing, associated with approximately doubled late-onset Alzheimer's disease risk in the discovery cohort (OR ~2.10) and a pooled OR of 1.53 in meta-analysis; replication has been inconsistent across large European cohorts.

Chromosome 19 Risk Allele A Category Neurology & Cognition Tags Alzheimer's, Neurodegeneration, Cognitive Decline, Autophagy, Brain Health, Dementia

Deep in the endolysosomes of every cortical and hippocampal neuron, a protein called PLD3 (phospholipase D family member 3) acts as a 5′ exonuclease — degrading single-stranded DNA and RNA that accumulates in the acidic lysosomal lumen. This housekeeping role prevents inflammatory nucleic acid signals from leaking...

rs1495377 Intronic variant in TSPAN8 (Tetraspanin 8) associated with reduced insulin secretion and type 2 diabetes risk; the G allele impairs pancreatic beta-cell and alpha-cell function, reducing insulinogenic response to glucose

Chromosome 12 Risk Allele G Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Pancreatic Beta Cell, Metabolic, Insulin Resistance, Metabolic Health

Tetraspanin 8 (TSPAN8) is a four-pass transmembrane glycoprotein that organizes proteins and lipids at the cell surface into signaling microdomains. While it is perhaps best known for its role in tumour biology, TSPAN8 is expressed in pancreatic islets where it plays a less-heralded but clinically meaningful role in...

rs162036 MTRR cobalamin-reactivation variant — reduces B12 recycling efficiency and modulates folate-therapy response

Chromosome 5 Risk Allele G Category Methylation & Detox Tags Methylation, B Vitamins, Homocysteine, Vitamin B12, Fertility, Methylation & Detox

Methionine synthase reductase (MTRR) is the enzyme that keeps the methylation cycle running by reactivating methionine synthase (MTR) after it becomes oxidized. MTR uses methylcobalamin(https://pubmed.ncbi.nlm.nih.gov/15979034/) to convert homocysteine into methionine, but that reaction periodically inactivates B12....

rs1797912 Intronic PPARG variant in the same haplotype block as rs1175543; the C allele is protective against metabolic syndrome (p=0.011) and was one of six PPARG SNPs significantly associated with body weight reduction during calorie restriction

Chromosome 3 Risk Allele A Category Fat Storage & Energy Tags Adipogenesis, Metabolic Syndrome, Metabolic Health, Fat Distribution, Obesity, Cardiovascular

The peroxisome proliferator-activated receptor gamma gene (PPARG) encodes PPARγ(https://www.ncbi.nlm.nih.gov/gene/5468), the most important transcription factor governing how precursor cells develop into fat cells and how sensitively those cells respond to insulin signals. rs1797912 sits in an intron of PPARG at...