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1.

Background

Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.

Methods

We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.

Results

We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values.

Conclusions

Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.  相似文献   

2.

Background

Biobehavioral correlates of self-rated health in pregnancy are largely unknown.

Purpose

The goals of this study were to examine, in pregnant women, associations of self-rated health with (1) demographics, objective health status, health behaviors, and psychological factors, and (2) serum inflammatory markers.

Methods

In the second trimester of pregnancy, 101 women provided a blood sample, completed measures of psychosocial stress, health status, and health behaviors, and received a comprehensive periodontal examination.

Results

The following independently predicted poorer self-rated health: (1) greater psychological stress, (2) greater objective health diagnoses, (3) higher body mass index, and (4) past smoking (versus never smoking). Poorer self-rated health was associated with higher serum interleukin-1β (p?=?0.02) and marginally higher macrophage migration inhibitory factor (p?=?0.06). These relationships were not fully accounted for by behavioral/psychological factors.

Conclusions

This study provides novel data regarding factors influencing subjective ratings of health and the association of self-rated health with serum inflammatory markers in pregnant women.  相似文献   

3.

Background

A genome-wide association study (GWAS) combined with brain imaging as a quantitative trait analysis revealed that the SNPs near CTXN3-SLC12A2 region were related to forebrain development and stress response which involved in schizophrenia. In the present study, the SNPs in this region were analyzed for association with schizophrenia in a Thai population.

Methods

A total of 115 schizophrenia and 173 unrelated normal controls with mean age of 37.87?±?11.8 and 42.81?±?6.0?years, respectively, were included in this study. Genotyping was performed using polymerase chain reaction and high-resolution melting (HRM) analysis. The difference in genotype distribution between patient and control was assessed by Chi-square test of the SPSS software.

Results

We found a significant association between the GWAS-discovered SNP, rs245178, with the risk of schizophrenia in the Thai population [P?=?0.006, odds ratio for the minor G allele: 0.62(0.46?C0.83)]. Additionally, another potential SNP, rs698172, which was in moderate linkage disequilibrium with rs245178, also showed strong association with schizophrenia [P?=?0.003, odds ratio for minor T allele: 0.61(0.46?C0.82)]. This association remained significant at 5% level after the Bonferroni correction for multiple testing.

Conclusions

This study shows that two SNPs in intergenic of the CTXN3 and SLC12A2 genes, rs245178 and rs698172, are associated with risk of schizophrenia in Thai population. Further study is required for clarification the role of genetic variation around these SNPs in expression pattern of the CTXN3 and SLC12A2 genes, which may be involved in schizophrenia pathogenesis.  相似文献   

4.

Background

Several lines of evidence indicate that the central cannabinoid receptor 1 (CNR1) as well as the major endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA) and monoglyceride lipase (MGLL) are implicated in mediating the orexigenic effects of cannabinoids. The aim of this study was to analyse whether nucleotide sequence variations in the CNR1, FAAH, NAAA and MGLL genes are associated with anorexia nervosa (AN).

Methods

We analysed the association of a previously described (AAT)n repeat in the 3' flanking region of CNR1 as well as a total of 15 single nucleotide polymorphisms (SNPs) representative of regions with restricted haplotype diversity in CNR1, FAAH, NAAA or MGLL in up to 91 German AN trios (patient with AN and both biological parents) using the transmission-disequilibrium-test (TDT). One SNP was additionally analysed in an independent case-control study comprising 113 patients with AN and 178 normal weight controls. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, ARMS-PCR or using 3730xl capillary sequencers.

Results

The TDT revealed no evidence for association for any of the SNPs or the (AAT)n repeat with AN (all two-sided uncorrected p-values > 0.05). The lowest p-value of 0.11 was detected for the A-allele of the CNR1 SNP rs1049353 for which the transmission rate was 59% (95% confidence interval 47%...70%). Further genotyping of rs1049353 in 113 additional independent patients with AN and 178 normal weight controls could not substantiate the initial trend for association (p = 1.00).

Conclusion

As we found no evidence for an association of genetic variation in CNR1, FAAH, NAAA and MGLL with AN, we conclude that genetic variations in these genes do not play a major role in the etiology of AN in our study groups.  相似文献   

5.

Background

There is an established link between socioeconomic status (SES) and performance of health behaviors with more health protective and fewer health-risking behaviors in higher SES groups.

Purpose

This research is novel in testing the moderating effect of SES on the relationship among intention, self-efficacy, and subsequent behavior.

Methods

Effects were tested on data from three prospective correlational studies examining smoking initiation in adolescents (N?=?826), breastfeeding in primiparous women (N?=?202), and physical activity in working adults (N?=?509).

Results

Despite examining different behaviors, samples, time intervals, and measures of SES, each study showed significant interactions between intention and SES in predicting behavior. In all three tests, the intention–behavior relationship was attenuated among individuals from lower SES groups. No moderation effects of SES were found for self-efficacy.

Conclusions

The intention–health behavior relationship can be attenuated in lower SES samples. This finding may contribute to our understanding of SES differences in health behaviors.  相似文献   

6.

Background

Preference for fatty foods is a risk factor for obesity. It is a complex behaviour that involves the brain reward system and is regulated by genetic and environmental factors, such as the opioid receptor mu-1 gene (OPRM1) and prenatal exposure to maternal cigarette smoking (PEMCS). We examined whether OPRM1 and PEMCS interact in influencing fat intake and whether exposure-associated epigenetic modifications of OPRM1 may mediate this gene–environment interaction.

Methods

We studied adolescents from a French Canadian genetic founder population, half of whom were exposed prenatally to maternal cigarette smoking. Fat intake was assessed with a 24-hour food recall in the form of a structured interview conducted by a trained nutritionist. The OPRM1 variant rs2281617 was genotyped for the whole sample with the Illumina Human610-Quad and HumanOmniExpress BeadChips. Methylation of blood DNA was assessed at 21 CpGs across OPRM1 in a subset of the sample using the Illumina HumanMethylation450 BeadChip.

Results

We included 956 adolescents in our study. In the whole sample, OPRM1 (T carrier in rs2281617) was associated with lower fat intake (−1.6%, p = 0.017), and PEMCS was associated with higher fat intake (+1.6%, p = 0.005). OPRM1 and PEMCS interacted with each other (p = 0.003); the “protective” (fat intake–lowering) allele of OPRM1 was associated with lower fat intake in nonexposed (−3.2%, p < 0.001) but not in exposed individuals (+0.8%, p = 0.42). Further, PEMCS was associated with lower DNA methylation across multiple CpGs across OPRM1 in exposed versus nonexposed individuals (p = 0.031).

Limitations

A limitation of our study was its cross-sectional design.

Conclusion

Our study suggests that PEMCS may interact with OPRM1 in increasing fat preference. Silencing of the protective OPRM1 allele in exposed adolescents might be related to epigenetic modification of this gene.  相似文献   

7.

Background

Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression.

Methods

We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes.

Results

We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification.

Conclusion

Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases.  相似文献   

8.

Background

Frizzled 3 (Fzd3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia.

Methods

Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls.

Results

A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis.

Conclusion

Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis.  相似文献   

9.

Purpose

Moyamoya is the most common cerebrovascular disease in children in Japan. The disease's etiology is still widely unknown. Several publications describe histopathological changes in the walls of affected vessels similar to those seen in atherosclerosis. In this study, we analyzed the DNA of European patients with Moyamoya disease for single nucleotide polymorphisms associated with atherosclerotic changes.

Methods

We genotyped 17 SNPs in or adjacent to 11 genes (ELN, LIMK1, CDKN2A/B, CXCL12, Pseudogene ENSG00000197218, PSRC1, MTHFD1L, SMAD3, MIA3, PDGF-B, TIMP2) comparing 40 DNA samples of Moyamoya disease patients to 68 healthy controls from central Europe. The mean age of onset of Moyamoya disease (MMD)-related symptoms was 15.4?years of age. Genotyping was performed by sequencing the SNP containing genetic regions with custom-made primers.

Results

We found strong association of one SNP (rs599839 [A/G], OR?=?2.17, 95% CI?=?1.17, 4.05; p?=?0.01) with the risk allele G located in the 3?? UTR region of the PSRC-1 gene. Three further SNPs (rs8326, rs34208922, rs501120) in or adjacent to the genes ELN and CXCL12 showed tendencies towards risk alleles with p values between 0.1 and 0.2 but did not reach statistical significance in our cohort.

Conclusions

Our results indicate a possible parallel of common processes in the genesis of Moyamoya disease and atherosclerotic disease. Further analyses in larger European cohorts and replication in patients of different ethnicity may lead to possible early detection of patients at risk for developing MMD and subsequently to future causative therapies.  相似文献   

10.

Background

Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia.

Method and Results

Eight single nucleotide polymorphisms (SNPs) were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (p corrected = 0.0072). This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis.

Conclusion

Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.  相似文献   

11.

Background

Approximately half of high school students in the USA have used tobacco. Social anxiety can put adolescents at increased risk for smoking.

Purpose

This study aims to determine whether adolescents high in trait social anxiety report more cigarette use and greater urge to smoke before, during, and after friend interactions than do teens low in trait social anxiety.

Methods

Four hundred two students who reported smoking more than once during high school were assessed approximately every 30?min during up to 84-day monitoring sessions.

Results

Controlling for momentary anxiety, high socially anxious teens were equally or less likely to smoke, but more likely to report urge to smoke, surrounding friend interactions than low socially anxious teens.

Conclusions

Although high socially anxious adolescents do not smoke more than low socially anxious peers, they may believe that they should need a cigarette in anxiety-provoking situations. Such urges may later develop into smoking behaviors.  相似文献   

12.

Background

Social cohesion, the self-reported trust and connectedness between neighbors, may affect health behaviors via psychosocial mechanisms.

Purpose

Relations between individual perceptions of social cohesion and smoking cessation were examined among 397 Black treatment-seeking smokers.

Methods

Continuation ratio logit models examined the relation of social cohesion and biochemically verified continuous smoking abstinence through 6 months post-quit. Indirect effects were examined in single mediator models using a nonparametric bootstrapping procedure. All analyses controlled for sociodemographics, tobacco dependence, and treatment.

Results

The total effect of social cohesion on continuous abstinence was non-significant (β?=?0.05, p?=?0.10). However, social cohesion was associated with social support, positive affect, negative affect, and stress, which, in turn, were each associated with abstinence in adjusted models (ps?<?0.05).

Conclusions

Results suggest that social cohesion may facilitate smoking cessation among Black smokers through desirable effects on psychosocial mechanisms that can result from living in a community with strong interpersonal connections.  相似文献   

13.

Background

Objective, subjective, and neighborhood socioeconomic status (SES) are associated with perceived health, morbidity, and mortality.

Purpose

We investigated whether perceived stress and health behaviors mediated the relation between the three types of SES and perceived health.

Methods

Participants (N?=?508) attending a public clinic completed a computerized survey assessing objective SES (income, education, employment); health behaviors; perceived stress; and perceived health. They also indicated their social standing relative to others (subjective SES) and provided their current address to determine neighborhood SES.

Results

In a structural equation model including all three SES types, lower objective and subjective SES were related to poorer perceived health. When mediators were included in the model, there were significant indirect effects of (a) SES on health through stress and (b) SES on health through stress and health-compromising behaviors.

Conclusions

Interventions to reduce the impact of stressors could improve the health of socioeconomically disadvantaged individuals.  相似文献   

14.

Background

Identifying characteristics that influence smoking behavior among military personnel is critical to protect health and operational functioning.

Purpose

This study prospectively examined rates of cigarette smoking and predictors of changes in smoking behavior as a function of Iraq deployment.

Methods

One thousand eighty-two US Army soldiers (n?=?773 Iraq-deployed; n?=?309 nondeployed) completed assessments at two sessions [time 1: April 2003–July 2004; time 2: May 2004–July 2004 (nondeployers); January 2005–September 2006 (deployers)].

Results

Approximately 48 % of participants smoked at both time points, with 6 % initiating smoking and 6 % quitting. Smoking initiation was associated with warzone stress exposure; female gender and high military unit support predicted cessation. Military rank and alcohol use were associated with both smoking initiation and cessation.

Conclusion

Findings highlight the potential benefits of targeting risk factors for cigarette smoking in comprehensive military health programs aimed at smoking prevention and cessation.  相似文献   

15.

Background

Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.

Methods

We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.

Results

Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the SPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the TGFBI and SMAD5 genes and rs6897690 is within the SPRY4 gene.

Conclusion

Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.
  相似文献   

16.

Background

Post-myocardial infarction (MI) depression and anxiety were found to predict prognosis and quality of life.

Purpose

The purpose of this study was to test a behavioral pathway from post-MI depression/anxiety to future quality of life.

Methods

This is a longitudinal cohort study. Five hundred forty patients (≤65 years old) filled out questionnaires after a first MI, including socio-demographics, pre-MI health status and behaviors, MI severity, social support, sense of coherence, depression, and anxiety. Reports of health behaviors were obtained 5 years and of quality of life 10 years later.

Results

A structural equations model confirmed that depression and anxiety were directly related to poorer quality of life 10 years later. These relationships were partly mediated by a positive association between anxiety and health behaviors at 5 years and a negative one between depression and health behaviors.

Conclusions

The opposite effects of anxiety and depression underscore the need to attend to both emotional reactions to MI while encouraging preventive health behaviors.  相似文献   

17.

Background

There are almost no data on whether the different channels through which pro-smoking media appear (i.e., point-of-sale advertising, movie smoking) differently influence smoking.

Purpose

This study used ecological momentary assessment to examine whether differences in smoking risk were observed for exposures to different pro-smoking media channels.

Methods

College students (n?=?134) carried smartphones for 21 days, recording their exposures to pro-smoking media and the media channels for that exposure and responding to three randomly issued control prompts per day. Participants answered questions about their future smoking risk after each pro-smoking media exposure and random prompt.

Results

Participants had elevated future smoking risk following exposure to pro-smoking media at point of sale (p?<?0.001); smoking risk at times of exposure to smoking in movies did not differ from risk measured during control prompts (p?=?0.78).

Conclusions

There is merit to examining the relative contribution of different pro-smoking media channels to smoking behavior.  相似文献   

18.

Objective

Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (ABCC8) on the development of CE. We hypothesize that ABCC8 single nucleotide polymorphisms (SNPs) are predictive of CE.

Methods

DNA was extracted from 385 patients. SNPs in ABCC8 were genotyped using the Human Core Exome v1.2 (Illumina). CE measurements included acute CT edema, mean and peak intracranial pressure (ICP), and need for decompressive craniotomy.

Results

Fourteen SNPs with minor allele frequency >0.2 were identified. Four SNPS rs2283261, rs3819521, rs2283258, and rs1799857 were associated with CE measures. In multiple regression models, homozygote-variant genotypes in rs2283261, rs3819521, and rs2283258 had increased odds of CT edema (OR 2.45, p = 0.007; OR 2.95, p = 0.025; OR 3.00, p = 0.013), had higher mean (β = 3.13, p = 0.000; β = 2.95, p = 0.005; β = 3.20, p = 0.008), and peak ICP (β = 8.00, p = 0.001; β = 7.64, p = 0.007; β = 6.89, p = 0.034). The homozygote wild-type genotype of rs1799857 had decreased odds of decompressive craniotomy (OR 0.47, p = 0.004).

Conclusions

This is the first report assessing the impact of ABCC8 genetic variability on CE development in TBI. Minor allele ABCC8 SNP genotypes had increased risk of CE, while major SNP alleles were protective—potentially suggesting an evolutionary advantage. These findings could guide risk stratification, treatment responders, and the development of novel targeted or gene-based therapies against CE in TBI and other neurological disorders.
  相似文献   

19.

Background

Bipolar disorder is a widespread and severe brain disorder that is strongly affected by genetic factors. The PDZ and LIM domain 5 (PDLIM5) gene encodes a protein as an Enigma homologue LIM domain protein, which has been widely reported as being expressed in various brain regions. The analysis of DNA microarrays in the frontal lobes of patients with bipolar disorder has indicated changes in the expression level of PDLIM5, and subsequent studies have suggested that PDLIM5 might play a role in susceptibility to bipolar disorder. We sought to examine the association between PDLIM5 and bipolar disorder.

Methods

We recruited 502 patients with bipolar disorder and 507 controls from Anhui Province, China. We conducted a case–control study of 4 single-nucleotide polymorphisms (SNPs) of PDLIM5 that have been reported to be significantly associated with bipolar disorder in the Japanese and Chinese population: rs10008257, rs2433320, rs2433322 and rs2438146.

Results

We found that rs2433322 showed significantly different frequencies between patients and controls (p = 0.002). Three of the SNPs, rs10008257, rs2433320 and rs2438146, showed no statistical association with bipolar disorder; however, haplotypes constructed from 3 SNPs, rs2433320, rs2433322 and rs2438146, were significantly associated with bipolar disorder (global p = 0.004 after Bonferroni correction).

Limitations

Our genetic association study only offered evidence for susceptibility of PDLIM5 to bipolar disorder, but the positive SNP rs2433322 could not indicate a direct cause of this complicated brain disorder. In addition, the 4 tagged SNPs that we selected could not cover the whole region of PDLIM5, thus additional reproducible studies of more SNPS in large non-Asian populations are needed.

Conclusion

Our results suggest that PDLIM5 might play a role in susceptibility to bipolar disorder among the Chinese Han population.  相似文献   

20.
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