| 1 | J Neural Transm (Vienna) 2002 Feb 109: 213-8 |
|---|---|
| PMID | 12075862 |
| Title | Association study of C825T polymorphism of the G-protein b3 subunit gene with schizophrenia and mood disorders. |
| Abstract | Alterations of G proteins have been implicated in major psychiatric illnesses. A C825T polymorphism of a gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3) was reported to be associated with several pathological conditions, such as hypertension and depressive disorder. We examined whether this polymorphism is associated with functional psychoses in a Japanese sample of 370 schizophrenics, 164 bipolars, 68 depressive patients, and 198 controls. We obtained no evidence for an association of the polymorphism with any diagnostic group. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | J Neural Transm (Vienna) 2002 Feb 109: 213-8 |
| PMID | 12075862 |
| Title | Association study of C825T polymorphism of the G-protein b3 subunit gene with schizophrenia and mood disorders. |
| Abstract | Alterations of G proteins have been implicated in major psychiatric illnesses. A C825T polymorphism of a gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3) was reported to be associated with several pathological conditions, such as hypertension and depressive disorder. We examined whether this polymorphism is associated with functional psychoses in a Japanese sample of 370 schizophrenics, 164 bipolars, 68 depressive patients, and 198 controls. We obtained no evidence for an association of the polymorphism with any diagnostic group. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Neuropsychobiology 2004 -1 50: 37-40 |
| PMID | 15179018 |
| Title | Association study of adrenergic beta3 receptor (Trp64Arg) and G-protein beta3 subunit gene (C825T) polymorphisms and weight change during clozapine treatment. |
| Abstract | Weight gain, a common adverse effect of clozapine, may impair health and affect patient compliance during treatment with this agent. The aim of this study was to investigate the relationship between genetic variants of the adrenergic beta3 receptor (ADRB3) and the G-protein beta3 subunit (GNB3) and clozapine-induced body weight change (BWC). Eighty-seven treatment-resistant schizophrenic patients were weighed before and after 4 months of clozapine treatment, with the subjects gaining an average of 2.6 kg in body weight. No statistically significant relationship was demonstrated for the investigated ADRB3 Trp64Arg and the GNB3 C825T polymorphisms in terms of BWC post-treatment, suggesting these two polymorphisms do not play a significant role in clozapine-induced BWC. Further exploration of other genetic variants implicated in clozapine-induced BWC is important, however, in order to predict and reduce clozapine-associated weight gain. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Eur Neuropsychopharmacol 2005 Oct 15: 525-31 |
| PMID | 16139171 |
| Title | Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. |
| Abstract | G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (p<0.01 and p=0.03, respectively), with estimated effect sizes ranging from 4.8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Eur Neuropsychopharmacol 2005 Oct 15: 525-31 |
| PMID | 16139171 |
| Title | Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. |
| Abstract | G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (p<0.01 and p=0.03, respectively), with estimated effect sizes ranging from 4.8 to 7%. Our results further suggest that this effect is only attributable to Caucasians when compared to African-Americans. Moreover, our findings point to the role of intracellular mechanisms in antipsychotic response. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Pharmacogenomics 2006 Sep 7: 863-87 |
| PMID | 16981847 |
| Title | Genetics of antipsychotic treatment emergent weight gain in schizophrenia. |
| Abstract | Classic and modern antipsychotics can induce substantial weight gain causing diabetes, lipid abnormalities and psychological distress. Treatment emergent weight gain varies within the broad class of antipsychotics; however, an individual's propensity to develop weight gain largely depends on genetic factors. The first part of this review highlights current ideas and concepts related to antipsychotic-induced weight gain, including principles on energy homeostasis. The second part summarizes genetic findings emphasizing studies published after 2003 as prior studies have been reviewed in detail elsewhere. Candidate gene studies have produced significant findings in the 5-hydroxytryptamin 2C (5HT2C) and adrenergic alpha2a (ADRalpha2a) receptor genes, as well as in the leptin, guanine nucleotide binding protein (GNB3) and synaptomal-associated protein 25kDa (SNAP25) genes. Results from genome-wide association and linkage studies point to several chromosomal regions (e.g., 12q24) and some specific genes (e.g., promelanin concentrating hormone [PMCH], polycyctic kidney and hepatic disease 1 [PKHD1], peptidylglycine alpha-amidating monooxygenase [PAM]). However, more efforts are needed before risk prediction and personalized medicine can be made available for antipsychotic-induced weight gain. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Med. Sci. Monit. 2006 Feb 12: BR47-50 |
| PMID | 16449941 |
| Title | Pilot study of the G-protein beta3 subunit gene (C825T) polymorphism and clinical response to olanzapine or olanzapine-related weight gain in persons with schizophrenia. |
| Abstract | Despite advances in schizophrenia treatment, nearly 30% of patients do not respond to atypical antipsychotic agents, such as olanzapine. Furthermore, 30-60% of patients will gain significant weight during the course of olanzapine therapy. Little research has been done to investigate the relationship between antipsychotic treatment outcomes and genetic variability in second messengers coupled to serotonin (5HT) receptors. The purpose of this investigation was examine associations between the second messenger G-Protein Beta3 Subunit Gene (GNB3) C825T polymorphism and olanzapine response and weight gain treatment. We conducted a pharmacogenetic association study to examine GNB3 genotypes in relation to olanzapine clinical response (as measured by the Brief Psychiatric Rating Scale or Scale for the Assessment of Negative Symptoms) or weight gain. Subjects included forty-two individuals meeting DSM-IV criteria for schizophrenia that started olanzapine, were titrated to a fixed dose for 6 weeks, and subsequently genotyped for this investigation. No statistically significant associations existed between our outcome variables and GNB3 genotypes. However we did observe trends suggesting a potential relationship between the TT genotype, response, and weight gain that warrant further investigation. Preliminary results showed no statistical relationship between the C825T polymorphism and olanzapine response or weight gain. Numerical differences in outcome measures between the TT vs. CT/CC genotype groups indicate that G-protein second messenger systems variability coupled to primary targets of atypical antipsychotics may relate to clinical outcomes in persons with schizophrenia and that future research in this area is warranted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | Acta Neuropsychiatr 2007 Dec 19: 351-6 |
| PMID | 26953000 |
| Title | Possible association between G-protein ?3 subunit C825T polymorphism and antipsychotic-induced restless legs syndrome in schizophrenia. |
| Abstract | The incidence of restless legs syndrome (RLS) is presumed to be higher among people with schizophrenia who take antipsychotic medication, most of which blocks the dopamine D2 receptor. The purpose of this study was to determine whether the G-protein ?3 subunit (GNB3) C825T polymorphism is associated with antipsychotic-induced RLS in schizophrenia. We examined 178 Korean patients with schizophrenia. All of the subjects were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group and the International Restless Legs Scale. Genotyping was performed for the C825T polymorphism in the GNB3 gene. The genotype distribution did not differ significantly between antipsychotic-induced RLS patients and patients who had no-RLS symptoms (? 2 = 4.30, p = 0.116). The genotypes of the C825T single-nucleotide polymorphism (SNP) were classified into two groups: C+ (CC and CT genotypes) and C- (TT genotype). The presence of the C allele (C+) was associated with an increased likelihood of RLS (? 2 = 4.14, p = 0.042; odds ratio = 2.56, 95% confidence interval = 1.02-6.47). These results suggest that the GNB3 C825T SNP is associated with RLS in schizophrenia. However, confirming this association requires future larger scale studies in which the effects of medication are strictly controlled. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | Hum Psychopharmacol 2007 Dec 22: 501-4 |
| PMID | 17726725 |
| Title | No evidence for an association between G protein beta3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia. |
| Abstract | Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. We evaluated candidate functional polymorphism of the G protein beta3 subunit (GNB3) gene for association with drug-induced TD in the Korean schizophrenic patients. We investigated whether the C825T polymorphism of the GNB3 gene is associated with the TD in a Korean sample of schizophrenic patients with (n = 83) and without TD (n = 126), matched for antipsychotic drug exposure and other relevant variables. The distribution of genotypes and allele frequencies of GNB3 were not different between schizophrenic patients with TD and without TD (p > 0.05). Within the limitations imposed by the size of the clinical sample, these findings suggest that the GNB3 825 C/T single nucleotide polymorphism (SNP) does not contribute significantly to risk for TD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Hum Psychopharmacol 2007 Dec 22: 501-4 |
| PMID | 17726725 |
| Title | No evidence for an association between G protein beta3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia. |
| Abstract | Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. We evaluated candidate functional polymorphism of the G protein beta3 subunit (GNB3) gene for association with drug-induced TD in the Korean schizophrenic patients. We investigated whether the C825T polymorphism of the GNB3 gene is associated with the TD in a Korean sample of schizophrenic patients with (n = 83) and without TD (n = 126), matched for antipsychotic drug exposure and other relevant variables. The distribution of genotypes and allele frequencies of GNB3 were not different between schizophrenic patients with TD and without TD (p > 0.05). Within the limitations imposed by the size of the clinical sample, these findings suggest that the GNB3 825 C/T single nucleotide polymorphism (SNP) does not contribute significantly to risk for TD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | BMC Psychiatry 2007 -1 7: 22 |
| PMID | 17521439 |
| Title | Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach. |
| Abstract | schizophrenia is a common psychiatric disease affecting about 1% of population. One major problem in the treatment is finding the right the drug for the right patients. However, pharmacogenetic results in psychiatry can seldom be replicated. We selected three candidate genes associated with serotonergic neurotransmission for the study: serotonin 2A (5-HT2A) receptor gene, tryptophan hydroxylase 1 (TPH1) gene, and G-protein beta-3 subunit (GNB3) gene. We recruited 94 schizophrenia patients representing extremes in treatment response to typical neuroleptics: 43 were good responders and 51 were poor responders. The control group consisted of 392 healthy blood donors. We do, in part, replicate the association between 5-HT2A T102C polymorphism and response to typical neuroleptics. In female patients, C/C genotype was significantly more common in non-responders than in responders [OR = 6.04 (95% Cl 1.67-21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46-11.84), p = 0.005]. TPH1 A779C C/A genotype was inversely associated with good treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36-0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23-0.86, p = 0.016], and GNB3 C825T C/T genotype showed a trend-like positive association among the male patients with a good response compared with non-responders [OR = 3.48 (95% Cl 0.92-13.25), p = 0.061], and a clearer association when compared with the controls [OR = 4.95 (95% CI 1.56-15.70), p = 0.004]. More findings on the consequences of functional polymorphisms for the role of serotonin in the development of brain and serotonergic neurotransmission are needed before more detailed hypotheses regarding susceptibility and outcome in schizophrenia can be formulated. The present results may highlight some of the biological mechanisms in different courses of schizophrenia between men and women. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 12 | J Clin Psychiatry 2008 Sep 69: 1416-22 |
| PMID | 19193342 |
| Title | Multiple genetic factors in olanzapine-induced weight gain in schizophrenia patients: a cohort study. |
| Abstract | One of the clinically significant adverse effects of olanzapine treatment is weight gain, which shows substantial inter-individual differences and may be influenced by genetic variation. The aim of this investigation was identification of genetic risk factors associated with olanzapine-induced weight gain. Inpatients with DSM-IV-TR schizophrenia (N = 164) were administered olanzapine for 8 to 24 (mean +/- SD = 17.9 +/- 9.4) weeks. The clinical background, body mass index (BMI), and clinical response to olanzapine were investigated. Twenty-one loci of diverse candidate genes encoding dopamine, serotonin (5-HT), histamine, and adrenergic receptors, tumor necrosis factor-alpha, ghrelin, adiponectin, and peroxisome proliferator-activated receptor gamma-2, were analyzed. The study was conducted from June 2001 to June 2003 at 4 psychiatric hospitals in Japan. BMI increased by a mean +/- SD 4.3 +/- 10.7% after treatment with olanzapine (mean +/- SD dose = 15.5 +/- 5.8 mg/day). Olanzapine-induced weight gain correlated negatively with baseline BMI and positively with clinical global improvement and the length of olanzapine treatment (p < .0001), but it did not correlate with the daily dose of olanzapine, concomitant antipsychotics, sex, age, or smoking. Four genetic variants, the 102T allele of HTR2A, the 825T allele of GNB3, the 23Cys allele of HTR2C, and the 64Arg/Arg genotype of ADRB3, were significantly associated with olanzapine-induced weight gain. Stepwise regression analysis revealed that the baseline BMI predicted 12.5% of the weight gain, and the 2 latter genetic factors added 6.8%. The patients with double and triple genetic risk factors showed 5.1% and 8.8% BMI increases, respectively, during olanzapine treatment, whereas the patients with a single or no risk factor showed approximately a 1% BMI increase. We identified genetic variants of 5-HT(2A) and 5-HT(2C) receptors, the G-protein beta-3 subunit, and the adrenergic receptor beta-3, as genetic risk factors for olanzapine-induced weight gain, and they showed additive genetic effects on weight gain. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 13 | Pharmacogenomics 2008 Oct 9: 1429-36 |
| PMID | 18855531 |
| Title | G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics. |
| Abstract | Clozapine treatment of schizophrenia is effective only in 30-60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia. In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR. Homozygosity for the T825 allele was more frequent among nonresponders (chi(2) = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (chi(2) = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression. Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 14 | Pharmacogenomics 2008 Oct 9: 1429-36 |
| PMID | 18855531 |
| Title | G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics. |
| Abstract | Clozapine treatment of schizophrenia is effective only in 30-60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia. In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR. Homozygosity for the T825 allele was more frequent among nonresponders (chi(2) = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (chi(2) = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression. Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 15 | Pharmacogenomics 2008 Oct 9: 1429-36 |
| PMID | 18855531 |
| Title | G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics. |
| Abstract | Clozapine treatment of schizophrenia is effective only in 30-60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia. In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR. Homozygosity for the T825 allele was more frequent among nonresponders (chi(2) = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (chi(2) = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression. Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 16 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Dec 32: 1848-53 |
| PMID | 18793692 |
| Title | Association of antipsychotic induced weight gain and body mass index with GNB3 gene: a meta-analysis. |
| Abstract | It has been reported that C825T variant in the gene encoding the G-protein subunit beta3 (GNB3) is associated with antipsychotic-induced weight gain and obesity. We investigated the association of the GNB3 and antipsychotic-induced weight gain as well as body mass index (BMI) using meta-analytical techniques. Our analysis of 402 schizophrenia subjects showed a trend (p=0.072) only under a fixed-model. As it was observed heterogeneity among the studies (p=0.007), we re-analyzed using a random-effects framework and no significance was found (p=0.339). No evidence for bias publication was reported (p=0.868). Our analysis of 18,903 subjects showed a trend (p=0.053) associating CC and lower BMI under a fixed model. Although no significant association was found, the same pattern (CC and lower antipsychotic-induced weight gain) was observed. Our meta-analysis indicates that firmly establishing the role of pharmacogenetics in clinical psychiatry requires much larger sample sizes that have been reported. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 17 | Psychiatry Investig 2009 Mar 6: 39-43 |
| PMID | 20046372 |
| Title | G-protein beta3 Subunit Gene 825C/T Polymorphism Is Not Associated with Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients. |
| Abstract | Weight gain is a possible adverse effect of the use of antipsychotics, and is an important factor for long-term health and treatment compliance. Olanzapine is an atypical antipsychotic known to cause considerable weight gain. A relationship between weight gain and the G protein beta3 subunit gene (GNB3) 825C/T polymorphism has been reported. We therefore examined this possible association in a Korean schizophrenic patient group receiving olanzapine treatment. Weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the 825C/T polymorphism was performed using a PCR-based method. We found that long-term treatment with olanzapine resulted in mean gains in weight and body mass index (BMI) of 5.2 kg and 1.93 kg/m(2), respectively. There was a no significant difference in the mean body weight change from baseline to the endpoint after olanzapine treatment between the genotype groups (p=0.796). There were also no significant differences in genotype or allele frequencies between the severe weight-gain (more than 10%) and minimal weight-gain (less than 10%) groups (chi(2)=0.037, p=0.98; chi(2)=0.020, p=0.89). The finding from this study thus does not support a relationship between the GNB3 825C/T polymorphism and weight gain in Korean schizophrenic patients receiving olanzapine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 18 | Psychiatry Investig 2009 Mar 6: 39-43 |
| PMID | 20046372 |
| Title | G-protein beta3 Subunit Gene 825C/T Polymorphism Is Not Associated with Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients. |
| Abstract | Weight gain is a possible adverse effect of the use of antipsychotics, and is an important factor for long-term health and treatment compliance. Olanzapine is an atypical antipsychotic known to cause considerable weight gain. A relationship between weight gain and the G protein beta3 subunit gene (GNB3) 825C/T polymorphism has been reported. We therefore examined this possible association in a Korean schizophrenic patient group receiving olanzapine treatment. Weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the 825C/T polymorphism was performed using a PCR-based method. We found that long-term treatment with olanzapine resulted in mean gains in weight and body mass index (BMI) of 5.2 kg and 1.93 kg/m(2), respectively. There was a no significant difference in the mean body weight change from baseline to the endpoint after olanzapine treatment between the genotype groups (p=0.796). There were also no significant differences in genotype or allele frequencies between the severe weight-gain (more than 10%) and minimal weight-gain (less than 10%) groups (chi(2)=0.037, p=0.98; chi(2)=0.020, p=0.89). The finding from this study thus does not support a relationship between the GNB3 825C/T polymorphism and weight gain in Korean schizophrenic patients receiving olanzapine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 19 | Schizophr Bull 2016 May -1: -1 |
| PMID | 27217270 |
| Title | Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis. |
| Abstract | Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (?7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2-20, n = 81-2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values < .05-.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges' g's = 0.30-0.80, ORs = 1.47-1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1-2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |