Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia.
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ABSTRACT:
SUBMITTER: Arab AH
PROVIDER: S-EPMC4465678 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevious studies have suggested that the DRD2/ANKK1 rs1800497 C > T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C > T polymorphism and PTSD risk.Materials and methodsA total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power.ResultOverall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14-2.62, P = 0.01, I2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis.ConclusionCurrent evidence suggests that the DRD2/ANKK1 rs1800497 C > T polymorphism may contribute to PTSD susceptibility.
| S-EPMC10232825 | biostudies-literature
Project description:BackgroundThe clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia.MethodsThree SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity.ConclusionsThe results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.
| S-EPMC7302002 | biostudies-literature
Project description:ImportanceUrban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas.ObjectiveTo assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk.Design, setting, and participantsFour large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018.ExposuresPolygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models.Main outcomes and measuresPopulation density of the place of residence of the participants determined from census data. Remoteness and socioeconomic status of the area were also tested.ResultsThe QIMR participants (15 544; 10 197 [65.6%] women; mean [SD] age, 54.4 [13.2] years) living in more densely populated areas (people per square kilometer) had a higher genetic loading for schizophrenia (r2 = 0.12%; P = 5.69 × 10-5), a result that was replicated across all 3 other cohorts (UKB: 345 246; 187 469 [54.3%] women; age, 65.7 [8.0] years; NTR: 11 212; 6727 [60.0%] women; age, 48.6 [17.5] years; and QSKIN: 15 726; 8602 [54.7%] women; age, 57.0 [7.9] years). This genetic association could account for 1.7% (95% CI, 0.8%-3.2%) of the schizophrenia risk. Estimates from MR analyses performed in the UKB sample were significant (b = 0.049; P = 3.7 × 10-7 using GSMR), suggesting that the genetic liability to schizophrenia may have a causal association with the tendency to live in urbanized locations.Conclusions and relevanceThe results of this study appear to support the hypothesis that individuals with increased genetic risk tend to live in urban/dense areas and suggest the need to refine the social stress model for schizophrenia by including genetics as well as possible gene-environment interactions.
| S-EPMC6142911 | biostudies-literature
Project description:We investigated whether single nucleotide polymorphisms (SNPs) in the nuclear assembly factor 1 (NAF1) and TNFAIP3-interacting protein 1 (TNIP1) gene were associated with susceptibility to esophageal cancer in a Chinese Han population. Five SNPs were genotyped and their relationship with esophageal cancer risk was analyzed in a sample of 386 esophageal cancer patients and 495 unrelated healthy controls recruited from the First Affiliated Hospital of Xi'an Jiaotong University. Patients with the AG genotype of rs2320615 were at lower risk of developing esophageal cancer than those with the GG genotype (adjusted odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.46-0.90, P = 0.009). The rs2320615 SNP was found to be associated with a decreased the risk of esophageal cancer in the dominant model (adjusted OR = 0.70, 95% CI = 0.51-0.96, P = 0.026). These results provide the first evidence that the rs2320615 in NAF1 was associated with reduced risk of esophageal cancer. Further studies with larger samples are warranted to confirm our findings.
| S-EPMC5564553 | biostudies-literature
Project description:Schizophrenia is a polygenic disorder with many genomic regions contributing to schizophrenia risk. The majority of genetic variants associated with schizophrenia lie in the non-coding genome and are thought to contribute to transcriptional regulation. Extensive transcriptomic dysregulation has been detected from postmortem brain samples of schizophrenia-affected individuals. However, the relationship between schizophrenia genetic risk factors and transcriptomic features has yet to be explored. Herein, we examined whether varying gene expression features, including differentially expressed genes (DEGs), co-expression networks, and central hubness of genes, contribute to the heritability of schizophrenia. We leveraged quantitative trait loci and chromatin interaction profiles to identify schizophrenia risk variants assigned to the genes that represent different transcriptomic features. We then performed stratified linkage disequilibrium score regression analysis on these variants to estimate schizophrenia heritability enrichment for different gene expression features. Notably, DEGs and co-expression networks showed nominal heritability enrichment. This nominal association can be partly explained by cellular heterogeneity, as DEGs were associated with the genetic risk of schizophrenia in a cell type-specific manner. Moreover, DEGs were enriched for target genes of schizophrenia-associated transcription factors, suggesting that the transcriptomic signatures of schizophrenia are the result of transcriptional regulatory cascades elicited by genetic risk factors.
| S-EPMC8304922 | biostudies-literature
Project description:Although previous evidence has suggested that there is a genetic link between schizophrenia and creativity, the specific genetic variants that underlie the link are still largely unknown. To further explore the potential genetic link between schizophrenia and creativity, in a sample of 580 healthy Han Chinese subjects, this study aimed to (1) validate the role of Neuregulin 1 (NRG1) rs6994992 (one schizophrenia risk variant that has been previously linked to creativity in the European population) in the relationship between schizophrenia and creativity and (2) explore the associations between 10 other schizophrenia risk variants and creativity. For NRG1 rs6994992, the result validated its association with creativity measures. However, since NRG1 rs6994992 is not a schizophrenia risk variant in the Han Chinese population, the validated association suggested that ethnic difference may exist in the relationship between NRG1 rs6994992, schizophrenia and creativity. For other schizophrenia risk variants, the result only demonstrated a nominal association between ZNF536 rs2053079 and creativity measures which would not survive correction for multiple testing. No association between polygenic risk score for these 10 schizophrenia risk variants and creativity measures was observed. In conclusion, this study provides limited evidence for the associations between these schizophrenia risk variants and creativity in healthy Han Chinese subjects. Future studies are warranted to better understand the potential genetic link between schizophrenia and creativity.
| S-EPMC6792478 | biostudies-literature
Project description:Epidemiological studies have assessed the association between kallikrein 3 (KLK3) polymorphisms and prostate cancer (PCa) susceptibility. However, published data on this association are somewhat inconclusive. Articles investigating the association between three KLK3 (rs1058205, rs2735839, and rs266882) variants and PCa susceptibility were searched from online databases, which included 35,838 patients and 36,369 control participants. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to demonstrate the strength of the association. We also utilized ELISA to detect serum expression of KLK3. In addition, in silico tools were adopted to evaluate the relationship of KLK3 expression and PCa survival time. The overall results indicated that polymorphism T>C of rs1058205 was associated with decreased risk of PCa (allele contrast: OR = 0.75, 95% CI = 0.64-0.88, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.42-0.81, Pheterogeneity < 0.001), particularly in Caucasian population (allele contrast: OR = 0.77, 95% CI = 0.65-0.91, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.41-0.82, Pheterogeneity < 0.001). No association was observed between the polymorphism A>G of rs2735839 and risk of PCa. In addition, no association was observed between polymorphism A>G of rs266882 and risk of PCa. Serum KLK3 levels in PCa patients carrying CC/CT genotypes were statistically lower than those carrying TT genotypes. Conclusion: This meta-analysis suggests that rs1058205 polymorphism of KLK3 is a risk factor for PCa development, polymorphism T>C of rs1058205 is associated with decreased susceptibility to PCa particularly in Caucasian population.
| S-EPMC6265624 | biostudies-literature
Project description:Schizophrenia is a psychiatric syndrome that affects approximately 1 % of the world population and is among the top 10 reasons for disability. In this case-control study, we investigated the association between 15 insertion/deletion (Indel) polymorphisms and schizophrenia risk using pooled samples. In the present case-control study, 361 individuals with schizophrenia and 360 healthy individuals were included in the study. We examined the insertion/deletion polymorphisms in APOB, ADRA2B, PDCD6IP, LRPAP1, TLR2, DHFR, VEGF, HLA-G, TPA, DBH, UCP2, FADS2, MDM2, TP53 and SLC6A4 genes. Our results revealed that the Del allele of the HLA-G 14bp Indel polymorphism increased the risk of schizophrenia (OR=1.23, 95 % CI=1.01-1.52, p=0.045) and the Alu- allele of the TPA Alu+/Alu- polymorphism negatively associated with the schizophrenia risk (OR=0.67, 95 % CI=0.54-0.82, p<0.001).
| S-EPMC10201014 | biostudies-literature
Project description:Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate. We analyzed the largest genome-wide association studies of schizophrenia and lung, breast, prostate, ovary, and colon-rectum cancer including more than 220,000 subjects, and included genetic association with smoking behavior. Polygenic enrichment of associations with lung cancer was observed in schizophrenia, and weak enrichment for the remaining cancer sites. After excluding the major histocompatibility complex region, we identified three independent loci jointly associated with schizophrenia and lung cancer. The strongest association included nicotinic acetylcholine receptors and is an established pleiotropic locus shared between lung cancer and smoking. The two other loci were independent of genetic association with smoking. Functional analysis identified downstream pleiotropic effects on epigenetics and gene-expression in lung and brain tissue. These findings suggest that genetic factors may explain partly the observed epidemiological association of lung cancer and schizophrenia.
| S-EPMC5766533 | biostudies-literature
Project description:BackgroundAssociations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments.MethodsWe examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences.ResultsHigher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk.ConclusionGenetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.
| S-EPMC9226384 | biostudies-literature