rs334558

This is a regulatory region variant variant in the GSK3B gene.

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GWAS Catalog Trait Associations (4)

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

total cholesterol measurement

Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.02
p 1.0e-18
N 480,086
Large GWAS
multi-ancestry
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 0.02
p 6.0e-18
N 394,642
Large GWAS
European

low density lipoprotein cholesterol 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 0.02
p 4.0e-12
N 394,642
Large GWAS
European
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.02
p 5.0e-12
N 416,487
Large GWAS
multi-ancestry
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ClinVar annotation

Benign★★★☆
2 submitters1 publication
View on ClinVar →
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Research that mentions this SNP (5)

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Neuroplasticity and second messenger pathways in antidepressant efficacy: pharmacogenetic results from a prospective trial investigating treatment resistance
AssociationN=2,066Chiara Fabbri et al.(2017)· European Archives of Psychiatry and Clinical Neuroscience

A prospective pharmacogenetic study of 220 treatment-resistant depression (TRD) patients examined 50 tag SNPs in 14 neuroplasticity and second messenger pathway genes for association with antidepressant response. Key findings included replication of ZNF804A rs7603001 with venlafaxine response (OR=2.51), CREB1 rs2254137 with remission, CHL1 rs2133402 with lower TRD risk, and MAPK1 rs6928 with all phenotypes (p=0.0006 after Bonferroni). Pathway analysis in STAR*D (n=1846) identified protein processing in the endoplasmic reticulum pathway as a potential mechanism of MAPK1 involvement.

Traits studied:Antidepressant RemissionAntidepressant ResponseEscitalopram ResponseMajor Depressive DisorderTreatment-Resistant DepressionVenlafaxine Response
PubMedDOIMetascience Observatory
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Influence of neurexin 1 (NRXN1) polymorphisms in clozapine response
ReviewRenan P. Souza et al.(2010)· Human Psychopharmacology: Clinical and Experimental

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
PubMedDOIMetascience Observatory
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Association of GSK3β Polymorphisms With Brain Structural Changes in Major Depressive Disorder
AssociationN=149Becky Inkster et al.(2009)· Archives of General Psychiatry

A targeted sequencing study of 115 patients with bipolar disorder and depression identified genetic variants in NRG1, PIP4K2A, and HTR2C associated with treatment response and disease severity. The allele C of rs35641374 (NRG1) was associated with longer intervals between depressive episodes (p=4.37e-07), while the allele C of rs10508649 (PIP4K2A) was associated with longer intervals between manic/mixed episodes (p=0.000309) and treatment resistance assessed by CGI-I scale (p=0.000943). The allele A of rs2248440 (HTR2C) was associated with higher depression severity (p=0.003).

Traits studied:Antidepressant treatment responseBipolar affective disorderDepression severityDepressive episodeRecurrent depressive disorderTime to recurrence of depressive episodesTime to recurrence of manic/mixed episodes
PubMedDOIMetascience Observatory
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Focus on HTR2C: A possible suggestion for genetic studies of complex disorders
AssociationN=149Antonio Drago et al.(2009)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This targeted sequencing association study of 115 psychiatric patients and 34 controls identifies NRG1, PIP4K2A, and HTR2C as candidate biomarker genes for antidepressant treatment response and mood disorder recurrence. Key findings include rs35641374 (NRG1) associated with longer time to depressive recurrence in bipolar disorder (p=4.37e-07), rs61731109 and rs10508649 (PIP4K2A) associated with antidepressant non-response (p=0.00111 and p=0.000943), and rs2248440 (HTR2C) associated with higher depression severity (p=0.003).

Traits studied:Antidepressant treatment responseBipolar I disorderBipolar II disorderBipolar disorderDepression severityMajor depressive disorderRemission statusTime to recurrence of depressive episodeTime to recurrence of manic/mixed episode
PubMedDOIMetascience Observatory
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Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects
ReviewRenan P. Souza et al.(2009)· Human Psychopharmacology: Clinical and Experimental

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
PubMedDOIMetascience Observatory

About GSK3B

The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

View all GSK3B variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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