rs3813929

This is a upstream gene variant variant in the HTR2C gene.

Key Literature Trait Associations

Antipsychotic-Induced Weight Gain

HTR2C -759C>T (rs3813929) is a promoter variant in the serotonin 2C receptor gene on the X chromosome. The T allele is protective against antipsychotic-induced weight gain: a meta-analysis of 17 studies (n=3,170) found T carriers had significantly less weight gain (OR 0.34, 95% CI 0.20-0.57). The C allele (common, risk) predisposes to greater metabolic side effects with clozapine, olanzapine, and risperidone.

Allele C
OR 0.34
p 1.0e-4
Meta-analysis

Antipsychotic Weight Gain

HTR2C -759C>T is a promoter variant in the serotonin 2C receptor gene. The T allele is protective against antipsychotic-induced weight gain associated with clozapine, olanzapine, and risperidone, while the common C allele predisposes to greater metabolic side effects. Since antipsychotic-induced weight gain is a major cause of treatment non-adherence and cardiometabolic morbidity, this variant may help guide antipsychotic selection.

Zhang K et al. Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nature Structural & Molecular Biology 15(4):381-388 (2008)
Allele T
OR
p
Candidate gene study

ClinVar annotation

Likely Benign★★★
2 submitters1 publication
View on ClinVar →

Research that mentions this SNP (6)

Screening individuals with intellectual disability, autism and Tourette's syndrome for KCNK9 mutations and aberrant DNA methylation within the 8q24 imprinted cluster.
ReviewMarta Sánchez Delgado et al.(2014)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This review examines the genetic and epigenetic basis of Tourette Syndrome (TS), a neurodevelopmental disorder with high heritability (0.45-0.77). The paper reviews candidate gene associations including variants in SLITRK1 (rs9593835, rs9546538, rs9531520), DRD2/ANKK1 (rs1800497), ADORA1/ADORA2A (rs2228079, rs5751876), and other dopaminergic genes, along with a large GWAS in 1285 cases and 4964 controls highlighting rs7868992 in COL27A1. The review proposes that epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) may link genetic susceptibility with environmental factors in TS pathogenesis.

Traits studied:Gilles de la Tourette SyndromeTic disordersTicsTourette Syndrome
Converging Evidence for the Association of Functional Genetic Variation in the Serotonin Receptor 2a Gene With Prefrontal Function and Olanzapine Treatment
AssociationN=887Giuseppe Blasi et al.(2013)· JAMA Psychiatry

Association study of 55 SNPs in 887 Hungarian adults examining genetic predisposition to aggression measured by the Buss-Perry Aggression Questionnaire. The HTR2A rs7322347 intronic variant showed significant association with aggression after Bonferroni correction (p = 0.0007), with carriers of the minor A allele showing lower aggression levels. The DRD4 rs916455 variant also showed nominal significance (p = 0.0275) but did not survive multiple testing correction.

Traits studied:Aggressive behaviorAngerHostilityPhysical aggressionVerbal aggression
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
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
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
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

Gene information from NCBI Gene. Variant classifications from ClinVar.

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