Research — GeneOps

rs10489629 Intronic IL23R variant in LD block 2 where the T allele is associated with increased susceptibility to Crohn's disease and ankylosing spondylitis while the C allele is protective — a signal distinct from the rs1004819/rs7517847 haplotype block

Chromosome 1 Risk Allele T Category IBD & Mucosal Immunity Tags Inflammation, Autoimmune, IBD, Arthritis, Immune & Gut

The IL23R gene does not speak with one genetic voice. Scattered across a 36-kilobase region of chromosome 1, at least two independent haplotype blocks carry disease-associated variants that modulate interleukin-23 receptor activity through distinct mechanisms. rs10489629 sits in the larger of those blocks — LD block...

rs1060502576 Rare stop-gain variant in BMPR2 (p.Trp466Ter) that truncates the kinase domain via nonsense-mediated decay, causing haploinsufficiency and hereditary pulmonary arterial hypertension with incomplete penetrance and sex-dependent expression

Chromosome 2 Risk Allele A Category Vascular Inflammation & Remodeling Tags Cardiovascular, Heart Disease, Hypertension, Carrier Status, Genetic Counseling, Fibrosis

The tiny arteries that carry blood through the lungs depend on a protein called BMPR2(https://pubmed.ncbi.nlm.nih.gov/38716930/) to suppress abnormal muscle growth in the pulmonary artery walls. When this receptor is absent or defective, the pulmonary arteries gradually narrow — a process called pulmonary arterial...

rs10751659 Intronic variant in the PRG3 gene encoding eosinophil major basic protein homologue (MBPH/MBP-2) at chromosome 11q12.1; the rarer C allele tags variation in PRG3 expression and is associated with altered eosinophil granule protein activity implicated in allergic inflammation, IgE-mediated tissue damage, and atopic disease susceptibility

Chromosome 11 Risk Allele C Category Allergy & Atopic Disease Tags Asthma, Inflammation, Immune Response, Innate Immunity, Immune Function, IBD

Buried inside the granules of every activated eosinophil lies a pair of cationic proteins — twin weapons in the allergic immune arsenal. The better-known of the two is eosinophil major basic protein (MBP, encoded by PRG2), a highly positively charged protein that disrupts cell membranes, triggers mast cell...

rs10759931 Promoter variant in Toll-like receptor 4 that drives higher TLR4 expression and amplified innate immune signaling, increasing risk for atherosclerosis, diabetic retinopathy, and inflammatory tissue damage

Chromosome 9 Risk Allele G Category Innate Immunity & Infection Defense Tags TLR Signaling, Innate Immunity, Inflammation, Cardiovascular, Bacterial Sensing, Infection Risk

Toll-like receptor 4 is the innate immune system's primary alarm for Gram-negative bacteria and tissue damage. It scans for lipopolysaccharide (LPS)(https://www.omim.org/entry/603030) and signals from damaged cells. When TLR4 fires, it mobilizes the full inflammatory arsenal. This system must be calibrated precisely...

rs10786831 Intronic variant in the neurotrophin sorting receptor SORCS3, the top GWAS hit for major depression in the Howard et al. 2019 meta-analysis of 807,553 individuals; the G allele impairs glutamate receptor trafficking, fear extinction, and synaptic plasticity

Chromosome 10 Risk Allele G Category Mood & Behavior Tags Depression, Mood, Neuroplasticity, Brain Health, Anxiety, Neurotransmitters

In 2019, the largest genetic study of depression ever conducted — 807,553 individuals, 246,363 of them with depression — pointed to a single gene more strongly than any other: SORCS3(https://pubmed.ncbi.nlm.nih.gov/30718901/) The rs10786831 variant lies within an intron of SORCS3, in a position that likely...

rs10830963 Melatonin receptor variant that extends nighttime melatonin signaling in pancreatic beta cells, impairing glucose-stimulated insulin secretion — especially when meals are eaten late

Chromosome 11 Risk Allele G Category Hormones & Sleep Tags Sleep, Melatonin, Circadian, Diabetes, Insulin, Diet

The MTNR1B gene encodes melatonin receptor 1B() (MT2), a receptor found not only in the brain but also on the insulin-producing beta cells of the pancreas. This dual role places MTNR1B at the crossroads of two fundamental biological systems: the circadian clock and glucose metabolism. The rs10830963 variant sits in...

rs10838738 Intronic GWAS obesity variant in MTCH2 — affects mitochondrial energy balance, adipogenesis, and fatty acid oxidation through CPT1 regulation

Chromosome 11 Risk Allele G Category Appetite & Obesity Tags Obesity, Mitochondria, Energy Metabolism, Fat Metabolism, Adipogenesis, Metabolic

MTCH2 (Mitochondrial Carrier Homolog 2) encodes a protein embedded in the outer mitochondrial membrane that regulates how your cells burn fat versus store it. The rs10838738 variant is an intronic SNP that functions as a cis-eQTL(), increasing MTCH2 mRNA expression in adipose tissue. Higher MTCH2 levels tip the...

rs10848087 Synonymous variant in PIWIL1 associated with increased epithelial ovarian cancer risk in southern Chinese women; the AA genotype confers a roughly 5.7-fold elevated risk in case-control data.

Chromosome 12 Risk Allele A Category Fertility & Ovarian Function Tags Fertility, Ovarian Reserve, Cancer Risk, Cancer Screening, Genomic Stability, Women's Health

Most people have never heard of piRNAs(https://pubmed.ncbi.nlm.nih.gov/33718392/). Yet the protein that guides these tiny sentinels — PIWIL1, encoded on chromosome 12q24.33 — may influence a woman's lifetime risk of epithelial ovarian cancer (EOC). A 2023 three-center case-control study in southern China found that...

rs10848554 Intronic ADIPOR2 variant co-associated with cardiovascular disease risk in individuals with impaired glucose tolerance, tagging a haplotype of reduced hepatic adiponectin signaling through the ADIPOR2 locus

Chromosome 12 Risk Allele C Category Fat Storage & Energy Tags Adipogenesis, Cardiovascular, Fat Metabolism, Insulin Resistance, Metabolic Health, Omega-3

Adiponectin is one of the most abundant hormones secreted by fat tissue, with a critical and counterintuitive property: its levels fall as body fat increases, precisely when the body needs its metabolic protection most. Low circulating adiponectin is a consistent predictor of insulin resistance, type 2 diabetes,...

rs10852521 FTO intron 1 variant associated with BMI and body fat accumulation, with strongest effects seen in Hispanic and African American populations

Chromosome 16 Risk Allele C Category Fitness & Body Tags Fitness, Fat Distribution, Obesity, Metabolic, Diet, Exercise, Cardiovascular

The FTO (fat mass and obesity-associated) gene contains one of the most replicated loci in human obesity genetics. While the primary signal — tagged by rs9939609(https://pubmed.ncbi.nlm.nih.gov/17434869/) — sits in a regulatory cluster in intron 1 that controls IRX3/IRX5 expression in preadipocytes, the FTO locus...