Research — GeneOps

rs7850258 Intronic variant in the PTCSC2 lncRNA that alters a FOXE1 enhancer element, modulating thyroid gland development and hypothyroidism risk

Chromosome 9 Risk Allele G Category Hormones & Sleep Tags Hormones & Thyroid, Thyroid, Hormones, Fatigue, Metabolic Health

About 67.7 kilobases upstream of the FOXE1 gene — a master regulator of thyroid gland formation — sits a conserved enhancer element that fine-tunes how much FOXE1 protein the developing and adult thyroid produces. The rs7850258 variant sits inside this enhancer and changes which transcription factors can bind there....

rs324013 Promoter variant in STAT6 that alters transcription factor binding; the T allele is associated with reduced IFN-γ production in response to herpes simplex virus, forming a 6.87-kb haplotype with rs167769 that confers a 3.3-fold increased risk of eczema herpeticum in atopic dermatitis patients through enhanced Th2 signaling

Chromosome 12 Risk Allele T Category Allergy & Atopic Disease Tags JAK-STAT Signaling, Inflammation, Autoimmune, Asthma, Skin Health, T-Cell Regulation

STAT6 (Signal Transducer and Activator of Transcription 6)(https://pubmed.ncbi.nlm.nih.gov/19665768/) orchestrates the body's allergy response from a strategic position in the immune signaling hierarchy. The rs324013 variant sits in the promoter region of the STAT6 gene on chromosome 12q13 — approximately 7...

rs4851266 Intronic variant in the super elongation complex gene AFF3; the T allele increases AFF3 expression and was one of three original genome-wide significant hits for educational attainment (Rietveld 2013), with replication in all subsequent large GWAS

Chromosome 2 Risk Allele T Category Neurology & Cognition Tags Cognition, Brain Health, Neuroplasticity, Omega-3, Memory

Deep inside chromosome 2 sits a variant that quietly helped usher in the modern genetics of intelligence. rs4851266() was one of just three genome-wide significant hits in the landmark 2013 GWAS by Rietveld and colleagues(https://pubmed.ncbi.nlm.nih.gov/23722424/) that mapped the genetics of educational attainment...

rs4997557 Rare CYP2A6 missense variant (p.Thr294Ile) that likely reduces nicotine-metabolising enzyme activity, affecting smoking behaviour, cessation pharmacotherapy response, and metabolism of letrozole and tegafur

Chromosome 19 Risk Allele A Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Smoking Related, Cancer Risk, Lung Cancer

CYP2A6 is the liver's primary nicotine-metabolising enzyme, responsible for converting approximately 80% of absorbed nicotine to cotinine. The rate at which your body clears nicotine after each cigarette determines how quickly cravings return, how many cigarettes you smoke per day, and how well nicotine replacement...

rs61886492 Reduces intestinal GCPII enzyme activity by 53%, paradoxically raising circulating folate and lowering homocysteine by slowing folate catabolism in the gut

Chromosome 11 Risk Allele G Category Methylation & Detox Tags Methylation, Folate, B Vitamins, Homocysteine, Cardiovascular

Before dietary folate from leafy greens, lentils, and liver can enter your bloodstream, it must first be stripped of its glutamate chain. In the intestinal brush border, FOLH1 (folate hydrolase 1, also called GCPII or glutamate carboxypeptidase II()) performs this essential cleavage step. The H475Y variant at...

rs653178 Pleiotropic 12q24 locus variant in SH2B3 (LNK) modulating JAK-STAT cytokine signaling, with associations spanning blood pressure, type 2 diabetes, celiac disease, and coronary artery disease

Chromosome 12 Risk Allele C Category Blood Sugar & Diabetes Tags Diabetes, Insulin Resistance, Blood Pressure, Cardiovascular, Autoimmune, Inflammation

The 12q24 chromosomal region is often called the most pleiotropic locus in the human genome — a single genomic neighbourhood whose variants have been credibly associated with type 2 diabetes, systolic blood pressure, celiac disease, coronary artery disease, rheumatoid arthritis, type 1 diabetes, chronic kidney...

rs78534766 Low-frequency missense variant in adenylyl cyclase 7 that reduces cAMP synthesis by 40%, skews immune cells toward a pro-inflammatory Th2 phenotype, and is the strongest non-HLA coding risk factor for ulcerative colitis and autoimmune thyroid disease

Chromosome 16 Risk Allele A Category Hormones & Sleep Tags Thyroid, Hormones & Thyroid, Autoimmune, Inflammation, Immune & Autoimmune, Immune Function

Every cell in your immune system uses cyclic AMP (cAMP) as a molecular brake pedal — a second messenger that dials down inflammatory activation and keeps immune responses proportionate. Adenylyl cyclase 7 (ADCY7) is the enzyme that produces cAMP in lymphocytes(https://www.ncbi.nlm.nih.gov/gene/113), myeloid cells,...

rs35699176 Nonsense variant truncating ZNF77 at codon 100, impairing bronchial epithelial barrier integrity and increasing susceptibility to Aspergillus fumigatus airway colonization

Chromosome 19 Risk Allele A Category Allergy & Atopic Disease Tags Lung Health, Asthma, Infection Risk, Immune Defense, Respiratory Infections, Inflammation

The bronchial epithelium is the first line of defense against airborne pathogens, including the ubiquitous mould Aspergillus fumigatus(https://pubmed.ncbi.nlm.nih.gov/30237437/). ZNF77 — zinc finger protein 77 — is a transcription factor expressed in bronchial epithelial cells that helps regulate the structural...

rs5030655 Frameshift deletion causing no enzyme function, defining poor metabolizer status for many drugs including codeine, tramadol, and antidepressants

Chromosome 22 Risk Allele - Category Pharmacogenomics Tags Drug Metabolism, Pain Medication, Antidepressants, Pharmacogenomics

CYP2D66 is one of the most clinically important no-function alleles of the highly polymorphic CYP2D6 gene. This variant is characterized by a single-nucleotide deletion in exon 3 (c.454del, legacy name 1707delT) causing a frameshift and premature truncation of the CYP2D6 protein , resulting in complete loss of...

rs56051278 Intronic variant in GPD2 (mitochondrial glycerol-3-phosphate dehydrogenase), second-strongest signal (P=1.5×10⁻²⁹) from the first-ever motion sickness GWAS; the G allele is in high LD with a missense variant that alters GPD2 enzyme activity and is linked to impaired glucose homeostasis during vestibular stress

Chromosome 2 Risk Allele G Category Neurology & Cognition Tags Brain Health, Mitochondria, Energy Metabolism, Digestive Health, Migraine, Insulin

One in three people experiences clinically significant motion sickness, yet the biological reasons have long been obscure. In 2015, Hromatka et al.(https://pubmed.ncbi.nlm.nih.gov/25628336/) published the first genome-wide association study of motion sickness in 80,494 individuals from 23andMe — and found 35...