Research — GeneOps

rs4841132 Near-gene PPP1R3B variant used as primary tagging SNP in the Stender 2018 study; minor A allele promotes hepatic glycogen accumulation, elevating liver enzymes and raising the risk of hepatic glycogenosis, non-alcoholic fatty liver disease, and gallstones

Chromosome 8 Risk Allele A Category Liver Fat Tags Fat Metabolism, Liver Health, Triglycerides, Diet, Insulin, Metabolic Syndrome

Most people associate liver disease with fat. Yet for carriers of the minor A allele at rs4841132, the primary problem begins one step earlier in liver metabolism: the regulation of glycogen() synthesis and breakdown. This variant is in complete linkage disequilibrium() with rs4240624, and the two positions tag the...

rs10925239 Deep intronic MTR variant associated with reduced cleft lip/palate risk via lower methionine synthase expression

Chromosome 1 Risk Allele T Category Methylation & Detox Tags Methylation, B Vitamins, Homocysteine, Folate

Methionine synthase (MTR) sits at the center of the one-carbon metabolism cycle, converting homocysteine() back into methionine using methylcobalamin (active B12) as a cofactor and 5-methylTHF (methylfolate) as the methyl donor. This reaction is critical for two reasons: it clears homocysteine and regenerates...

rs1111875 Primary tag SNP at the HHEX/IDE locus on chromosome 10q23, one of the earliest and most replicated T2D GWAS hits, linked to reduced HHEX expression, impaired beta-cell development, and blunted first-phase insulin secretion

Chromosome 10 Risk Allele C Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Pancreatic Beta Cell, Fasting Glucose, Metabolic

Among the first genes implicated in type 2 diabetes by genome-wide association studies, the HHEX/IDE locus(https://pubmed.ncbi.nlm.nih.gov/17293876/) has been replicated across dozens of populations and hundreds of thousands of participants. The SNP rs1111875 is the primary tag marker for this locus — in complete...

rs11650680 Intronic regulatory variant in the ORMDL3 17q21 haploblock; the C allele drives elevated ORMDL3 expression in airway epithelial cells and immune cells, increasing asthma susceptibility and total IgE levels; the T allele is protective

Chromosome 17 Risk Allele C Category Allergy & Atopic Disease Tags Asthma, Lung Health, Inflammation, Immune Response, Immune System, Respiratory Infections

The chromosome 17q21 locus is the most consistently replicated genetic risk region for childhood-onset asthma. The locus spans a dense 130-kb regulatory haploblock containing six genes — IKZF3, ZPBP2, GSDMB, ORMDL3, LRRC3C, and GSDMA — and harbors a cluster of correlated variants that collectively regulate ORMDL3...

rs11713169 Intronic variant in neuroligin 1, a postsynaptic cell adhesion molecule essential for excitatory synapse formation and NMDA-dependent plasticity; the C allele increases susceptibility to motion sickness and impairs habituation to repeated motion exposure at genome-wide significance (P=5.9×10⁻¹³)

Chromosome 3 Risk Allele C Category Neurology & Cognition Tags Cognition, Neuroplasticity, Sensory Processing, Brain Health, Neurotransmitters

About one in three people is highly susceptible to motion sickness. For decades this variation was assumed to be mostly psychological or a matter of inner-ear anatomy, but the first genome-wide association study of motion sickness(https://pubmed.ncbi.nlm.nih.gov/25628336/) — in 80,494 individuals from 23andMe —...

rs1175543 Intronic PPARG variant in strong linkage disequilibrium with rs709158; the G allele associates with a protective effect against metabolic syndrome and modestly lower total cholesterol in large prospective data.

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

Peroxisome proliferator-activated receptor gamma (PPARγ) is the master transcriptional regulator of fat cell development and a central node in insulin sensitivity(https://pubmed.ncbi.nlm.nih.gov/25366759/). rs1175543 is a common intronic variant in PPARG — one of several non-coding variants across the gene that tag...

rs121918390 Nonsense mutation truncating apolipoprotein B at residue 2522, causing familial hypobetalipoproteinemia with characteristically low LDL-C, hepatic steatosis, and potential fat-soluble vitamin insufficiency in heterozygous carriers

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

Apolipoprotein B (apoB) is the structural backbone of every LDL, VLDL, and chylomicron particle your liver makes. Without a full-length apoB-100, your liver cannot build and secrete normal LDL particles, so your circulating LDL cholesterol stays characteristically and permanently low(). This sounds like good news —...

rs12248560 Increased function CYP2C19 variant - rapid/ultrarapid metabolizer

Chromosome 10 Risk Allele T Category Pharmacogenomics Tags Drug Metabolism, Proton Pump Inhibitors, Antidepressants

While most pharmacogenomic attention focuses on loss-of-function variants, the CYP2C1917 allele| rs12248560 represents the opposite end of the spectrum: a gain-of-function variant that increases enzyme activity beyond normal levels. This variant sits in the promoter region and upregulates CYP2C19 gene expression....

rs1330 Intronic NUCB2 variant associated with obesity risk in males, type 2 diabetes risk in females, and colorectal cancer susceptibility — the T allele modestly affects nesfatin-1 signaling across multiple metabolic and oncological contexts

Chromosome 11 Risk Allele T Category Hormones & Sleep Tags Hormones, Sleep, Appetite, Obesity, Metabolic Health, Cancer Risk

Nucleobindin-2 (NUCB2) encodes the precursor protein that is proteolytically cleaved to release nesfatin-1(https://pubmed.ncbi.nlm.nih.gov/20682642/), a neuropeptide with broad roles in appetite suppression, glucose regulation, sleep-wake cycling, and — more recently discovered — cancer biology. The rs1330 variant...

rs1343151 Intronic IL23R variant whose minor A allele tags the protective haplotype for ankylosing spondylitis and Crohn's disease while representing an independent susceptibility signal for rheumatoid arthritis

Chromosome 1 Risk Allele A Category IBD & Mucosal Immunity Tags Autoimmune, Inflammation, IBD, Arthritis, T-Cell Regulation, Immune Function

The interleukin-23 receptor (IL23R) gene encodes a key checkpoint in adaptive immunity. When IL-23 binds IL23R on T helper 17 (Th17) cells, it triggers STAT3 phosphorylation(https://pubmed.ncbi.nlm.nih.gov/21364948/), sustaining chronic inflammation in the gut, spine, and skin. The rs1343151 variant sits in an...