{{Rsnum
|rsid=4606
|Gene=RGS2
|Chromosome=1
|position=192812042
|Orientation=plus
|GMAF=0.3508
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;G)
|geno3=(G;G)
|Gene_s=RGS2
}}In mice, the genetic locus best correlated to anxiety-related behaviour contains the 'regulator of G protein signaling 2' gene {{PMID|15489855}}. In humans, SNPs in the equivalent [[RGS2]] gene have now been studied to see if they are correlated to [[anxiety]] related disorders.{{PMID|18316676}}

In the first part of one study, 119 families including children underwent standard lab-based behavioural assessments of behavioural inhibition, defined as a heritable temperamental profile characterized by a tendency to be shy, avoident, and behaviourally restrained in situations that are novel or unfamiliar. Along with some other [[RGS2]] SNPs, carriers of a [[rs4606]](G) allele were 3 fold more likely to exhibit behavioural inhibition (CI: 1.31-6.84, p = 0.0026).

In the second part of this study, 744 college undergraduates (228 men, 516 women) who had been genotyped completed a [[personality]] profile known as the NEO-E (introversion) association test. Consistent with the earlier results, the same [[RGS2]] alleles associated with behavioural inhibition were significantly (p < 0.05) associated with introversion (but not neuroticism), including [[rs4606]](G), [[rs6428136]](G), and [[rs10801152]](T).

In the third part of this study, 55 female undergraduates were studied by fMRI (functional MRI) emotional processing tests. Carriers of SNPs [[rs4606]](G) or [[rs10801152]](T) showed increased insular cortex activation, a reflection of anxiety, in these tests.

Based on these results, the authors predict that [[social anxiety disorder]] is the most likely anxiety disorder to be associated with SNPs in the [[RGS2]] gene such as [[rs4606]]. 
 
{{PMID|18316676}} SNPs in the [[RGS2]] gene, including [[rs4606]], show association with childhood temperament, adult personality, and brain function.

{{PMID|18833580|OA=1
}} each [[rs4606]](C) allele was associated with a 2x (p =.026) increased risk of generalized anxiety disorder.

{{PMID|16736243}} 173 patients with panic disorder (and 173 matched controls) of German descent analyzed, leading to the conclusion that [[rs4606]](G) carriers were at ~2x increased risk for this disorder. Note that the (G) allele appears to be the minor (rarer) allele in this study.

'''Note:''' given the conflicting reports over whether the (C) or (G) allele is implicated in anxiety-related disorders, Dr. Jordan Smoller was contacted to verify that the orientation was unambiguously reported in the various publications. He has confirmed that the reports truly vary in which allele is considered the risk allele; this may be an example of the "flip-flop" phenomenon {{PMID|17273975|OA=1
}}.

[[rs4606]] has also been reported to be associated with the development of Parkinson's like symptoms in [[schizophrenia]] patients treated with various drugs, as follows:

{{PMID|18347610}} A replication study was performed in which extrapyramidal symptoms (EPS) were rated in 184 US patients with [[schizophrenia]]. This group (115 African Americans, 69 Caucasian) was treated for at least a month with typical antipsychotic drugs (n=45), [[risperidone]] (n=46), [[olanzapine]] (n=50) or [[clozapine]] (n=43). The minor (G) allele showed a protective effect against antipsychotic-induced parkinsonism (AIP), with an odds ratio for AIP among [[rs4606]](G) carriers of 0.23 (CI: 0.10-0.54, p=0.001) for the overall sample.

[http://genes2brains2mentalhealth.wordpress.com/2009/07/07/from-the-insula-rs4606-pulls-a-common-thread-back-through-developmental-space-and-time/ blog] discussion

{{PMID|17558307}} 121 consecutively hospitalized, psychotic patients with Diagnostic and Statistical Manual of Mental Disorder-IV [[schizophrenia]] receiving treatment with typical antipsychotic medication (n=72) or typical antipsychotic drugs and [[risperidone]] (n=49) for at least 2 weeks were studied. After correction for multiple testing the only [[RGS2]] SNP associated with development or worsening of parkinsonian symptoms was [[rs4606]] (p=0.002).

{{PMID|19162436|OA=1
}} rs4606 modifies risk of postdisaster and lifetime [[post-traumatic stress disorder]] symptoms under conditions of high stressor exposure
{{PMID Auto
|PMID=19156702
|Title=Lack of association between antipsychotic-induced Parkinsonism or its subsymptoms and rs4606 SNP of RGS2 gene in African-Caribbeans and the possible role of the medication: the Curacao extrapyramidal syndromes study X.
}}

{{PMID Auto
|PMID=19813112
|Title=Variation in RGS2 is associated with suicidal ideation in an epidemiological study of adults exposed to the 2004 Florida hurricanes
|OA=1
}}

{{PharmGKB
|RSID=rs4606
|Name_s=
|Gene_s=RGS2
|Feature=
|Evidence=PubMed ID:18347610
|Annotation=This variant is located in the 3'-regulatory region of RGS2, and is known to influence RGS2 mRNA levels and protein expression. It has been shown to be associated antipsychotic-induced parkinsonism (AIP) with possible protective effect of the minor G allele of rs4606.
|Drugs=clozapine; olanzapine; risperidone
|Drug Classes=
|Diseases=Parkinson Disease; Psychotic Disorders
|Curation Level=Curated
|PharmGKB Accession ID=PA164738462
}}

{{PMID Auto
|PMID=17728697
|Title=Association of RGS2 gene polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims.
}}

{{PMID Auto
|PMID=18262772
|Title=Association of RGS2 and RGS5 variants with schizophrenia symptom severity.
|OA=1
}}

{{PMID Auto
|PMID=19931593
|Title=Association analysis between functional polymorphism of the rs4606 SNP in the RGS2 gene and antipsychotic-induced Parkinsonism in Japanese patients with schizophrenia: results from the Juntendo University Schizophrenia Projects (JUSP).
}}

{{PMID Auto
|PMID=21438143
|Title=Association of RGS2 variants with panic disorder in a Japanese population.
}}

{{PMID Auto
|PMID=21737952
|Title=Genetic variation in gsalpha protein as a new indicator in screening test for vasovagal syncope.
}}

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs4606
|overall_frequency_n=43
|overall_frequency_d=128
|overall_frequency=0.335938
|n_genomes=33
|n_genomes_annotated=0
|n_haplomes=39
|n_articles=1
|n_articles_annotated=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23339167
|Title=Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia.
}}

{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}