rs2011425

This is a missense variant in the UGT1A4 gene.

Key Literature Trait Associations

Lamotrigine Metabolism

UGT1A4 P24T affects the glucuronidation rate of lamotrigine, the primary metabolic pathway for this anticonvulsant. Carriers may have altered lamotrigine clearance, leading to variable steady-state drug levels. Since UGT1A4 is the primary enzyme responsible for lamotrigine metabolism, this variant may be relevant for dose optimization, particularly in combination with valproate (which inhibits lamotrigine glucuronidation).

Pieri M et al. “Epirubicin permeation of personal protective equipment can induce apoptosis in keratinocytes.” Journal of Exposure Science & Environmental Epidemiology 23(4):428-434 (2013)

Allele A

OR —

p —

Candidate gene study

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GWAS Catalog Trait Associations (9)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

X-21441 measurement

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)

Allele G

OR 0.36

p 8.0e-39

N 8,030

Large GWAS

European

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)

Allele G

OR 0.29

p 4.0e-12

N 6,136

Large GWAS

European

vitamin D level

Manousaki D et al. “Genome-wide Association Study for Vitamin D Levels Reveals 69 Independent Loci.” American Journal of Human Genetics 106(3):327-337 (2020)

Allele G

OR 0.05

p 1.0e-37

N 443,734

Large GWAS

European

X-11440 measurement

Surendran P et al. “Rare and common genetic determinants of metabolic individuality and their effects on human health.” Nature Medicine 28(11):2321-2332 (2022)

Allele T

OR 0.19

p 9.0e-25

N 14,296

Large GWAS

European

metabolite measurement

Schlosser P et al. “Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.” Nature Genetics 55(6):995-1008 (2023)

Allele G

OR 0.36

p 8.0e-20

N 4,813

Large GWAS

European

pregnenetriol sulfate measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)

Allele G

OR 0.34

p 2.0e-16

N 6,136

Large GWAS

European

insulin-like 3 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele G

OR 0.06

p 2.0e-14

N 47,745

Large GWAS

European

pregnenetriol disulfate measurement

Yin X et al. “Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.” Nature Communications 13(1):1644 (2022)

Allele G

OR 0.30

p 3.0e-13

N 6,136

Large GWAS

European

Chen Y et al. “Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases.” Nature Genetics 55(1):44-53 (2023)

Allele G

OR 0.16

p 3.0e-10

N 8,228

Large GWAS

European

plasma N-desmethylclozapine measurement

Pardiñas AF et al. “Pharmacogenomic Variants and Drug Interactions Identified Through the Genetic Analysis of Clozapine Metabolism.” The American Journal of Psychiatry 176(6):477-486 (2019)

Allele G

OR —

p 8.0e-9

N 2,989

Large GWAS

European

testosterone measurement

Ruth KS et al. “Using human genetics to understand the disease impacts of testosterone in men and women.” Nature Medicine 26(2):252-258 (2020)

Allele T

OR 0.04

p 9.0e-25

N 382,988

Large GWAS

European

Haas CB et al. “Cross-ancestry Genome-wide Association Studies of Sex Hormone Concentrations in Pre- and Postmenopausal Women.” Endocrinology 163(4) (2022)

Allele T

OR 0.04

p 1.0e-8

N 182,648

Large GWAS

European

Harrison S et al. “Testosterone and socioeconomic position: Mendelian randomization in 306,248 men and women in UK Biobank.” Science Advances 7(31) (2021)

Allele T

OR 0.20

p 3.0e-10

N 148,248

Major Consortium StudyLarge GWAS

European

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Research that mentions this SNP (1)

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Interaction between genetic variants ofDLGAP3andSLC1A1Affecting the Risk of Atypical Antipsychotics‐Induced Obsessive–Compulsive Symptoms

AssociationN=91Seunghyong Ryu et al.(2011)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This proof-of-concept study examined polygenetic risk scores (PRS) in 91 clozapine-treated schizophrenia patients with obsessive-compulsive symptoms/disorder (OCS/OCD). OCS prevalence was 39.6% and OCD prevalence was 27.5%. A significant correlation was found between OCD occurrence and PRS for CLZ metabolism (p=0.010 at pd=0.001), though this did not survive multiple testing correction. OCS severity positively correlated with clozapine treatment duration and PANSS general psychopathology subscale scores, but no associations were found with PRS for OCD, schizophrenia, or cross-disorder phenotypes.

Traits studied:CLZ/NorCLZ ratioClozapine metabolismNorclozapine metabolismObsessive-compulsive disorderObsessive-compulsive symptomsSchizophrenia

rs2011425

Key Literature Trait Associations

Lamotrigine Metabolism

GWAS Catalog Trait Associations (9)

X-21441 measurement

vitamin D level

X-11440 measurement

metabolite measurement

pregnenetriol sulfate measurement

insulin-like 3 measurement

pregnenetriol disulfate measurement

plasma N-desmethylclozapine measurement

testosterone measurement

Research that mentions this SNP (1)

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