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1.

Background

Schizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment.

Methods

We analyzed 99 SNPs from 10 candidate genes in 1,512 subject samples. The permutation-based single-locus, multi-locus association tests, and a gene-based multifactorial dimension reduction procedure were used to examine genetic associations and interactions to schizophrenia.

Results

We found that no single SNP was significantly associated with schizophrenia. However, a risk haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene, was strongly associated with schizophrenia. Interaction analyses identified multiple between-gene and within-gene interactions. Between-gene interactions including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for CACNG2 were found among schizophrenia subjects with severe sustained attention deficits, suggesting a modifying effect of impaired neuropsychological functioning. Other interactions such as the within-gene interaction of DAO and the between-gene interaction of DAO and PTK2B were consistently identified regardless of stratification by neuropsychological dysfunction. Importantly, except for the within-gene interaction of CACNG2, all of the identified risk haplotypes and interactions involved SNPs from DAO.

Conclusions

These results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. Besides, the interaction between DAO and RASD2 has provided an insight in integrating the glutamate and dopamine hypotheses of schizophrenia.  相似文献   
2.
Haemophilus influenzae type b ATCC 10211 was cultured at different temperatures (25 degrees C-49 degrees C) and pH values (5.7-8.7) either in liquid or semisolid medium. Morphological variations of individual cells were noted by optical microscopy depending upon the conditions of growth. At higher temperatures filaments were produced whereby the length of individual cells increased compared to cultures grown at 37 degrees C. Filaments were also observed at lower pH values. Culture conditions also affected colonial morphology. At low pH values colonies had an enhanced lobulated contour and were more wrinkly and rougher than at higher pH. The changes in cellular and colonial morphology were correlated with distinct outer membrane protein profiles. The changes in temperature and pH did not affect identification of the microorganism by the API system.  相似文献   
3.
Schizophrenia is perhaps the most debilitating mental disease and determining the underlying cause has become a challenging area of psychiatric research. It is relatively well established that genes play a role in the aetiology of schizophrenia. In this article, a review of important findings related to schizophrenia as a genetic trait will be provided, including a discussion of family, twin and adoption studies. Molecular genetic studies of specific candidate genes are then reviewed. Some controversies within the literature are examined and possible directions for future research are discussed.  相似文献   
4.
We extend the methodology for family-based tests of association and linkage to allow for both variation in the phenotypes of subjects and incorporation of covariates into general-score tests of association. We use standard association models for a phenotype and any number of predictors. We then construct a score statistic, using likelihoods for the distribution of phenotype, given genotype. The distribution of the score is computed as a function of offspring genotypes, conditional on parental genotypes and trait values for offspring and parents. This approach provides a natural extension of the transmission/disequilibrium test to any phenotype and to multiple genes or environmental factors and allows the study of gene-gene and gene-environment interaction. When the trait varies among subjects or when covariates are included in the association model, the score statistic depends on one or more nuisance parameters. We suggest two approaches for obtaining parameter estimates: (1) choosing the estimate that minimizes the variance of the test statistic and (2) maximizing the statistic over a nuisance parameter and using a corrected P value. We apply our methods to a sample of families with attention-deficit/hyperactivity disorder and provide examples of how covariates and gene-environment and gene-gene interactions can be incorporated.  相似文献   
5.
6.
Biological invasions are regarded as a form of global change and potential cause of biodiversity loss. Xenopus laevis is an anuran amphibian native to sub-Saharan Africa with strong invasive capacity, especially in geographic regions with a Mediterranean climate. In spite of the worldwide diffusion of X. laevis, the effective impact on local ecosystems and native amphibian populations is poorly quantified. A large population of X. laevis occurs in Sicily and our main aim of this work was to assess the consequences of introduction of this alien species on local amphibian populations. In this study we compare the occurrence of reproduction of native amphibians in ponds with and without X. laevis, and before and after the alien colonization. The results of our study shows that, when X. laevis establishes a conspicuous population in a pond system, the populations of Discoglossus pictus, Hyla intermedia and Pelophylax synklepton esculentus show clear signs of distress and the occurrence of reproduction of these native amphibians collapses. In contrast, the populations of Bufo bufo do not appear to be affected by the alien species. Since the Sicilian population of X. laevis shows a strong dispersal capacity, proportionate and quick interventions become necessary to bound the detriment to the Sicilian amphibians populations.  相似文献   
7.
Numerical and experimental methods were employed to assess the individual and collective dosimetry of mice used in a bioassay on the exposure to pulsed radiofrequency energy at 900 MHz in the Ferris-wheel exposure system (Utteridge et al., Radiat. Res. 158, 357-364, 2002). Twin-well calorimetry was employed to measure the whole-body specific absorption rate (SAR) of mice for three body masses (23 g, 32 g and 36 g) to determine the lifetime exposure history of the mice used in the bioassay. Calorimetric measurements showed about 95% exposure efficiency and lifetime average whole-body SARs of 0.21, 0.86, 1.7 and 3.4 W kg(-1) for the four exposure groups. A larger statistical variation in SAR was observed in the smallest mice because they had the largest variation in posture inside the plastic restrainers. Infrared thermography provided SAR distributions over the sagittal plane of mouse cadavers. Thermograms typically showed SAR peaks in the abdomen, neck and head. The peak local SAR at these locations, determined by thermometric measurements, showed peak-to-average SAR ratios below 6:1, with typical values around 3:1. Results indicate that the Ferris wheel fulfills the requirement of providing a robust exposure setup, allowing uniform collective lifetime exposure of mice.  相似文献   
8.
This study evaluated whether showing a video of the different ways of raising goats for milk affected consumer acceptability. Four combinations, 2 Videos (intensive [INT] and semiextensive [SEM] system) × 2 Milk Types (semiskimmed [S] and whole [W] milk), were evaluated by 70 habitual consumers of goat milk, who scored their liking and purchase intention during blind (B), expected (E), and informed (I) acceptability sessions. In the B session, consumers tasted both milk types without information. S samples were preferred over W samples. In the E session, SEM video created high expectations in terms of milk liking and purchase intent, whereas the opposite happened when showing INT video. In the I session, consumers showed a clear preference for combinations created using SEM video, regardless of milk type. W-SEM and S-INT were worse (negative disconfirmation) and better (positive disconfirmation) than expected, respectively. A complete assimilation toward expectations occurred only for S-INT. INT video adversely affected the acceptability of S samples. Concerning purchase intent, W-SEM and S-SEM were worse than expected, but the assimilation was complete only for S-SEM: SEM video increased purchase intent for S samples.  相似文献   
9.
Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for eight neurocognitive test variables of the continuous performance test (CPT) and the Wisconsin card sorting test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms (SNPs) covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of nondeficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or nondeficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia.  相似文献   
10.
Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive–impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive–impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.  相似文献   
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