Dataset Information

Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia.

ABSTRACT: Limited research has assessed associations between schizophrenia and genetic variants of the ankyrin repeat and kinase domain containing 1 (ANKK1) and lymphotoxin-alpha (LTA) genes among individuals of Middle Eastern ancestry. Here we present the first association study investigating the ANKK1 rs1800497 (T>C) and LTA rs909253 (A>G) single-nucleotide polymorphisms in an Egyptian population. Among 120 patients with DSM-IV and PANSS (Positive and Negative Syndrome Scale) assessments of schizophrenia and 100 healthy controls, we determined the genotypes for the polymorphisms using endonuclease digestion of amplified genomic DNA. Results confirmed previous findings from different ethnic populations, in that the rs1800497 and rs909253 polymorphisms were both associated with risk of schizophrenia. Differences between the genotypes of cases and controls were strongly significant (P = 0.0005 for rs1800497 and P = 0.001 for rs909253). The relative risk to schizophrenia was 1.2 (P = 0.01) for the C allele and 0.8 (P = 0.04) for the G allele. The CC, GG, and combined CC/AA genotypes were all more frequent in cases than in controls. These results support an association between ANKK1 and LTA genetic markers and vulnerability to schizophrenia and show the potential influence of just one copy of the mutant C or G allele in the Egyptian population.

SUBMITTER: Arab AH

PROVIDER: S-EPMC4465678 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia.

Arab Arwa H AH Elhawary Nasser A NA

BioMed research international 20150531

Limited research has assessed associations between schizophrenia and genetic variants of the ankyrin repeat and kinase domain containing 1 (ANKK1) and lymphotoxin-alpha (LTA) genes among individuals of Middle Eastern ancestry. Here we present the first association study investigating the ANKK1 rs1800497 (T>C) and LTA rs909253 (A>G) single-nucleotide polymorphisms in an Egyptian population. Among 120 patients with DSM-IV and PANSS (Positive and Negative Syndrome Scale) assessments of schizophreni ...[more]

PMID: 26114114

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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.

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.

Dataset Information

Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia.

Publications

Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia.

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