The chemotherapeutic efficacy in colorectal cancer (CRC) is limited due to the inter-individual variability in drug response and the development of tumour resistance. ATP-binding cassette (ABC) transporters are crucial in the development of resistance by the efflux of anticancer agents from cancer cells. In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes acting as an expression of quantitative trait loci (eQTLs), i.e. whose variation influence the expression of many downstream genes. These SNPs were genotyped in a case-control study comprising 1098 cases and 1442 healthy controls and analysed in relation to CRC development risk and patient survival. Considering a strict correction for multiple tests, we did not observe any significant association between SNPs and CRC risk. The rs3819720 polymorphism in the ABCB3/TAP2 gene was statistically significantly associated with shorter overall survival (OS) in the codominant, and dominant models [GA vs. GG, hazard ratio (HR) = 1.48; P = 0.002; AA vs. GG, HR = 1.70; P = 0.004 and GA + AA vs. GG, HR = 1.52; P = 0.0006]. Additionally, GA carriers of the same SNP displayed worse OS after receiving 5-FU based chemotherapy. The variant allele of rs3819720 polymorphism statistically significantly affected the expression of 36 downstream genes. Screening for eQTL polymorphisms in relevant genes such as ABC transporters that can regulate the expression of several other genes may help to identify the genetic background involved in the individual response to the treatment of CRC patients.
- MeSH
- ATP-Binding Cassette Transporters blood genetics MeSH
- Databases, Genetic MeSH
- Fluorouracil therapeutic use MeSH
- Genotype MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms drug therapy genetics metabolism mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Quantitative Trait Loci MeSH
- Follow-Up Studies MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Rhizobacteria are root-associated bacteria that influence plant growth by various direct and indirect mechanisms. In quest of efficient plant growth-promoting rhizobacteria (PGPR) with multiple plant growth-promoting traits, a total of 52 rhizobacterial isolates were isolated from the rhizospheric soil collected at Pohang beach, Republic of Korea. The bacterial isolates were evaluated in vitro for their plant growth-promoting traits like production of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, indole-3-acetic acid (IAA), siderophore, and phosphate solubilization activities. More than 28% of the isolates revealed all of the multi-trait plant growth-promoting activities, whereas 11.54% exhibited robust results for producing IAA, ACC deaminase, siderophore, and phosphate solubilization activities. Similarly, 36% isolates were capable for the production of IAA, siderophore, and ACC deaminase, while 32% revealed phosphate solubilization and siderophore production. The isolates with prominent multi-trait plant growth-promoting activities were identified based on 16S rRNA gene sequences and matched to Pseudomonas koreensis-(S4T10), Pseudomonas fluorescens-(S3B1), Serratia fonticola-(S1T1), Sphingobacterium multivorum-(S1B1), Brevundimonas vesicularis-(S1T13), and Arthrobacter sp.-(S2T9) with 99-100% similarity. Our results confirm that further evaluation of these PGPR (exhibiting multi-traits for plant growth promotion) is required on crop plants to reveal their pragmatic role under normal and abiotic stress conditions and add into the consortium of biofertilizers for sustainable agriculture.
Trait anxiety is characterized as a constant and often subliminal state that persists during daily life. Interoception is the perception of internal states and sensations, including from the autonomic nervous system. This review aims to develop a predictive model to explain the emergence, manifestations, and maintenance of trait anxiety. The model begins with the assumption that anxiety states arise from active interoceptive inference. The subsequent activation of autonomic responses results from aversive sensory encounters. A cognitive model is proposed for trait anxiety that includes the aversive sensory components from interoception, exteroception, and proprioception. A further component of the hypothesis is that repeated exposure to subliminal anxiety-evoking sensory elements can lead to an overgeneralization of this response to other inputs that are generally non-aversive. Increased uncertainty may result when predicting the sensory environment, resulting in arbitrary interoceptive anxiety responses that may be due to unjustifiable causes. Arbitrary successful or unsuccessful matching of predictions and responses reduces the individual's confidence to maintain the anxiety trait. In this review, the application of the proposed model is illustrated using gut microbial dysbiosis or imbalance of the gut microbiome.
OBJECTIVE: Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta-analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs). METHODS: 322 participants with JME and 126 age and gender-matched controls completed the Barratt's Impulsiveness Scale (BIS-brief) alongside information on seizure history and AED use. We compared group BIS-brief scores and assessed associations of JME BIS-brief scores with seizure characteristics and AED adverse effects. RESULTS: The mean BIS-brief score in JME was 18.1 ± 4.4 compared with 16.2 ± 4.1 in controls (P = 0.0007). Elevated impulsivity was associated with male gender (P = 0.027), frequent absence seizures (P = 0.0004) and lack of morning predominance of myoclonus (P = 0.008). High impulsivity significantly increased the odds of a psychiatric adverse event on levetiracetam (P = 0.036), but not any other psychiatric or somatic adverse effects. INTERPRETATION: Trait impulsivity is elevated in JME and comparable to scores in personality and neurotic disorders. Increased seizure frequency and absence of circadian seizure pattern moderate BIS score, suggesting disruption of both cortico-striatal and thalamocortical networks as a shared mechanism between seizures and impulsivity in JME. These findings warrant consideration of impulsivity as a distinct target of intervention, and as a stratifying factor for AED treatment in JME, and perhaps other types of epilepsy. The role of impulsivity in treatment adherence and psychosocial outcome requires further investigation.
- MeSH
- Child MeSH
- Adult MeSH
- Impulsive Behavior * MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Myoclonic Epilepsy, Juvenile psychology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10-10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
- MeSH
- Alleles MeSH
- Genome-Wide Association Study * MeSH
- Carcinoma, Pancreatic Ductal genetics MeSH
- Genetic Predisposition to Disease * MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Quantitative Trait Loci * MeSH
- Pancreatic Neoplasms genetics MeSH
- GTPase-Activating Proteins genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
- MeSH
- Bipolar Disorder genetics MeSH
- Genome-Wide Association Study * MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease MeSH
- Genome, Human MeSH
- Major Histocompatibility Complex genetics MeSH
- Humans MeSH
- Chromosomes, Human genetics MeSH
- Quantitative Trait Loci genetics MeSH
- Multifactorial Inheritance genetics MeSH
- Risk Factors MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Research Support, N.I.H., Extramural MeSH
DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 × 10-7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 × 10-6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10-4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.
- MeSH
- Deoxyribonuclease I metabolism MeSH
- Genetic Predisposition to Disease * MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Quantitative Trait Loci MeSH
- Lung Neoplasms genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
- MeSH
- Genome-Wide Association Study * MeSH
- Adult MeSH
- Mental Disorders complications genetics MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease * MeSH
- Genomics methods MeSH
- Body Mass Index MeSH
- Humans MeSH
- Quantitative Trait Loci * MeSH
- Anorexia Nervosa etiology genetics pathology MeSH
- Metabolic Diseases complications genetics MeSH
- Prognosis MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.
- MeSH
- White People genetics MeSH
- Genome-Wide Association Study * MeSH
- Genetic Predisposition to Disease * MeSH
- Polymorphism, Single Nucleotide * MeSH
- Carcinoma, Renal Cell * genetics MeSH
- Humans MeSH
- Quantitative Trait Loci * MeSH
- Von Hippel-Lindau Tumor Suppressor Protein genetics MeSH
- Kidney Neoplasms * genetics MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
Cíl: Cílem této studie bylo zhodnotit frekvenci výskytu depresivních a úzkostných poruch u pacientů po operaci syndromu karpálního tunelu ve srovnání s normálními jedinci. Materiál a metody: Jedná se o průřezovou analytickou studii případů a kontrol prováděnou na pacientech, kteří podstoupili operaci s diagnózou syndromu karpálního tunelu. V první skupině bylo náhodně vybráno 35 pacientů se syndromem karpálního tunelu, kteří podstoupili operaci a byla u nich vyhodnocena úzkost a deprese pomocí dvou standardních dotazníků: CES-D (Center for Epidemiologic Studies Depression) a S-TAI (Spielberger State-Trait Anxiety Inventory). Druhá skupina 35 normálních lidí byla náhodně vybrána a vyšetřena ve shodě věku a pohlaví. Data byla porovnána a analyzována pomocí softwaru SPSS V.22. Výsledky: Průměrné skóre Spielbergerova stavu a rysu úzkosti a deprese v případové skupině bylo vyšší než u kontrolní skupiny (p < 0,001 a p = 0,003). V obou věkových skupinách (< 40 a > 40 let) byla míra stavové a rysové úzkosti a deprese signifikantně vyšší než u kontrolní skupiny. U žen byla míra stavové a povahové úzkosti a deprese signifikantně vyšší v případové skupině než u kontrolní skupiny, ale u mužů byla významná pouze povahová úzkost. Závěr: Úzkostné a depresivní poruchy byly častější u pacientů se syndromem karpálního tunelu než u normálních jedinců. Proto je nutné studovat psychický stav těchto pacientů v období před propuštěním a věnovat pozornost jeho prediktorům za účelem plánování vhodných intervencí.
Purpose: The aim of this study was to evaluate the frequency of depressive and anxiety disorders in patients with carpal tunnel syndrome (CTS) after surgery in comparison with normal individuals. Materials and methods: This cross-sectional analytical case-control study conducted on patients who underwent surgery with a diagnosis of carpal tunnel syndrome. In the first group, 35 patients with CTS who underwent surgery were randomly selected and evaluated for anxiety and depression with two standard questionnaires – of CES-D (Center for Epidemiologic Studies Depression) and S-TAI (Spielberger State-Trait Anxiety Inventory). The second group of 35 normal people were randomly selected and examined after matching the age and sex. The data were compared and analyzed using SPSS V.22 software. Results: The mean score of Spielberger state and trait anxiety and depression in the case group was higher than the control group (P < 0.001 and P = 0.003 respectively). In both age groups (< 40 and > 40 years) the level of state and trait anxiety and depression was significantly higher in case than the control group. In women, the level of state and trait anxiety and depression was significantly higher in the case group than in the control group, but in men, only trait anxiety was significant. Conclusion: The anxiety and depression disorders were more common in patients undergoing CTS than in normal individuals. Therefore, it is necessary to study the psychological status of these patients in the pre-discharge period and pay attention to its predictors in order to plan appropriate interventions.
