BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09). DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

• MeSH
• celogenomová asociační studie metody   MeSH
• diabetes mellitus * genetika   MeSH
• genetická predispozice k nemoci MeSH
• interakce genů a prostředí MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   MeSH
• lidé MeSH
• mikrofilamentové proteiny genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• LRCH1 protein, human MeSH Prohlížeč
• mikrofilamentové proteiny MeSH

Understanding the formation of risk preferences is crucial for elucidating the roots of economic, social, and health inequalities. However, this area remains inadequately explored. This study employs a risk preference measure directly linked to the labor market to examine whether previous experiences with high unemployment rates influence current risk decision-making among the elderly, and whether this impact varies by genotype. The findings indicate that individuals with low genetic predispositions for risk tolerance are more significantly influenced by historical fluctuations in unemployment rates than those with high genetic predispositions for risk tolerance. Consequently, this paper identifies genetic endowment as a crucial moderating factor that shapes how past experiences impact current decision-making processes. This disparity in how past experiences shape risk preferences based on genetic predisposition may further amplify inequalities in health, wealth, income, and other outcomes associated with risk preferences.

• Klíčová slova
• Human capital, Polygenic scores, Risk preferences, Unemployment rate,
• MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• interakce genů a prostředí * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nezaměstnanost * psychologie   MeSH
• postoj MeSH
• riskování MeSH
• rozhodování MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Genetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored. METHODS: We therefore superimposed maternal separation (MS) onto a genetic rat model (Flinders-sensitive and -resistant lines, FSL/FRL) of depression, treated these rats with antidepressants (escitalopram and nortriptyline) and measured CGRP-LI in selected brain regions. RESULTS: CGRP was elevated in the frontal cortex, hippocampus and amygdala (but not in the hypothalamus) of FSL rats. However, MS did not significantly alter levels of this peptide. Likewise, there were no significant interactions between the genetic and environmental factors. Most importantly, neither escitalopram nor nortriptyline significantly altered brain CGRP levels. CONCLUSION: Our data demonstrate that increased brain levels of CGRP are present in a well-established rat model of depression. Given that antidepressants have virtually no effect on the brain level of this peptide, our study indicates that further research is needed to evaluate the functional role of CGRP in the FSL model for depression.

• Klíčová slova
• Flinders-sensitive line, calcitonin gene-related peptide, escitalopram, maternal deprivation, nortriptyline,
• MeSH
• amygdala účinky léků   metabolismus   MeSH
• antidepresiva farmakologie   MeSH
• čelní lalok účinky léků   metabolismus   MeSH
• citalopram farmakologie   MeSH
• deprese * farmakoterapie   etiologie   metabolismus   MeSH
• hipokampus účinky léků   metabolismus   MeSH
• interakce genů a prostředí * MeSH
• krysa rodu Rattus MeSH
• maternální deprivace * MeSH
• modely nemocí na zvířatech MeSH
• mozek * účinky léků   metabolismus   MeSH
• nortriptylin farmakologie   MeSH
• peptid spojený s genem pro kalcitonin * účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• citalopram MeSH
• nortriptylin MeSH
• peptid spojený s genem pro kalcitonin * MeSH

BACKGROUND: Occupational exposures are known risk factors for lung cancer. Role of genetically determined host factors in occupational exposure-related lung cancer is unclear. METHODS: We used genome-wide association (GWA) data from a case-control study conducted in 6 European countries from 1998 to 2002 to identify gene-occupation interactions and related pathways for lung cancer risk. GWA analysis was performed for each exposure using logistic regression and interaction term for genotypes, and exposure was included in this model. Both SNP-based and gene-based interaction P values were calculated. Pathway analysis was performed using three complementary methods, and analyses were adjusted for multiple comparisons. We analyzed 312,605 SNPs and occupational exposure to 70 agents from 1,802 lung cancer cases and 1,725 cancer-free controls. RESULTS: Mean age of study participants was 60.1 ± 9.1 years and 75% were male. Largest number of significant associations (P ≤ 1 × 10(-5)) at SNP level was demonstrated for nickel, brick dust, concrete dust, and cement dust, and for brick dust and cement dust at the gene-level (P ≤ 1 × 10(-4)). Approximately 14 occupational exposures showed significant gene-occupation interactions with pathways related to response to environmental information processing via signal transduction (P < 0.001 and FDR < 0.05). Other pathways that showed significant enrichment were related to immune processes and xenobiotic metabolism. CONCLUSION: Our findings suggest that pathways related to signal transduction, immune process, and xenobiotic metabolism may be involved in occupational exposure-related lung carcinogenesis. IMPACT: Our study exemplifies an integrative approach using pathway-based analysis to demonstrate the role of genetic variants in occupational exposure-related lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 24(3); 570-9. ©2015 AACR.

• MeSH
• celogenomová asociační studie metody   MeSH
• genotyp MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic epidemiologie   etiologie   genetika   MeSH
• nemoci z povolání epidemiologie   etiologie   genetika   MeSH
• pracovní expozice škodlivé účinky   statistika a číselné údaje   MeSH
• rizikové faktory MeSH
• signální transdukce MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

• MeSH
• dieta MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• index tělesné hmotnosti MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   epidemiologie   MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• pití alkoholu MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Mental disorders affect about one-third of the human population, are typically chronic and significantly decrease the quality of life. Presently, the treatment of mental illnesses is far from adequate with a substantial proportion of the patients being pharmacoresistant and suffering from relapses. One of the reasons for this complicated situation is that we do not precisely know about the causes of mental disorders, so their treatment cannot be causal. The etiology of a mental disorder is typically based on a combination of molecular (genetic) and environmental factors. AIM: The aim of the project is to discover the gene-environment interactions (GxE) in a wide spectrum of mental disorders. METHODS: The design of our study is innovative in the sense that we intend to study large groups of associated mental disorders as a whole instead of in isolation. This would enable us to map out the possible environmental causal factors in detail in relation to their character, magnitude and timing. The project also allows a study of genetics (including epigenetics and microbiomes) as well as the environment simultaneously. We plan on involving three study groups: the first group are patients suffering from schizophrenia or a mood disorder such as major depression, recurrent depressive disorder and bipolar affective disorder; the second group of patients have anxiety disorders; and the third group are healthy volunteers from the general population who are genetically unrelated. All of the study subjects will undergo the following assessments: a psychiatric examination, the identification of stressful life events with the aid of a questionnaire, the examination of their reaction to stress, genetic and epigenetic (microRNA) assessments and the analysis of oral and gut microbiome. CONCLUSION: We expect that some of the genetic as well as environmental factors in the studied mental disorders are shared, while some others are specific. We also expect that the GxE (gene-environment interaction) in schizophrenic and affective disorders will be different from the GxE in anxiety disorders and that the GxE in the studied mental disorders will differ generally from the GxE in healthy volunteers. Our results can help in the prevention and individualized treatment of a range of mental disorders.

• Klíčová slova
• GxE interactions, anxiety disorders, environment, gene, mood disorders, schizophrenia,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Alcohol intake and tobacco smoking have significant negative health consequences and both are influenced by genetic predispositions. Some studies suggest that the FTO gene is associated with alcohol consumption. We investigated whether a tagging variant (rs17817449) within the FTO gene is associated with alcohol intake, problem drinking and smoking behaviour. METHODS: We analysed data from 26,792 Caucasian adults (47.2% of males; mean age 58.9 (±7.3) years), examined through the prospective cohort HAPIEE study. The primary outcomes were daily alcohol consumption, binge drinking, problem drinking (CAGE score 2+) and smoking status in relation to tagging variants within the FTO and ADH1B genes. RESULTS: We found no significant association of the FTO polymorphism with smoking status in either sex. The associations of the FTO polymorphism with drinking pattern were inconsistent and differed by gender. In men, GG homozygote carriers had lower odds of problem drinking (OR 0.85, 95% CI 0.75-0.96, p = 0.03). In women, the combination of the FTO/ADH1B GG/+A genotypes doubled the risk of binge drinking (OR 2.10, 95% CI 1.19-3.71, p < 0.05), and the risk was further increased among smoking women (OR 4.10, 95% CI 1.64-10.24, p = 0.008). CONCLUSIONS: In this large population study, the FTO gene appeared associated with binge and problem drinking, and the associations were modified by sex, smoking status and the ADH1B polymorphism.

• Klíčová slova
• ADH1B, Alcohol intake, Binge drinking, FTO, Polymorphism, Sex, Smoking,
• MeSH
• alkoholdehydrogenasa genetika   MeSH
• alkoholismus genetika   MeSH
• běloši genetika   MeSH
• gen pro FTO genetika   MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• interakce genů a prostředí MeSH
• jednonukleotidový polymorfismus * MeSH
• kouření genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nárazové pití alkoholu genetika   MeSH
• pití alkoholu genetika   MeSH
• prospektivní studie MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADH1B protein, human MeSH Prohlížeč
• alkoholdehydrogenasa MeSH
• FTO protein, human MeSH Prohlížeč
• gen pro FTO MeSH

Most contemporary models of disease development consider the interaction between genotype and environment as static. The authors argue that because time is a key factor in genotype-environment interaction, this approach oversimplifies the pathology analysis and may lead to wrong conclusions. In reviewing the field, the authors suggest that the history of genotype-environment interactions plays an important role in the development of diseases and that this history may be analyzed using the phenotype as a proxy. Furthermore, a theoretical and experimental framework is proposed based on the assumption that phenotypes do not change from one to another randomly but are interconnected and follow certain phenotype trajectories. It then follows that analysis of such phenotype trajectories might be useful to predict the future phenotypes including the onset of disease. In addition, an analysis of phenotype trajectories can be subsequently used to choose better control subjects in comparative studies reducing noise and bias in studies investigating disease mechanisms.

• Klíčová slova
• disease, environment, health, pathosome, phenotype, preconditioning,
• MeSH
• čas MeSH
• epidemiologické metody MeSH
• genetická predispozice k nemoci MeSH
• genetická variace MeSH
• genotyp * MeSH
• interakce genů a prostředí * MeSH
• lidé MeSH
• modely genetické * MeSH
• nemoc genetika   MeSH
• patologie metody   MeSH
• stárnutí genetika   MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Gene-environment interactions have been investigated for diseases such as asthma, chronic obstructive pulmonary disease, cancer etc. but acute disease like bronchitis has rarely been studied. We investigated interactions between air pollution (polycyclic aromatic hydrocarbons (PAH) and particulate matter <2.5 μm (PM2.5)) and single nucleotide polymorphisms (SNP) in EPHX1, IL10, STAT4 and XPC genes in relation to bronchitis in children aged 0-2 years. METHODS: A stratified random sample of 1133 Czech children, born between 1994 and 1998 in two districts, were followed since birth, of which 626 were genotyped. Pediatrician-diagnosed bronchitis episodes were obtained from the medical records. Central-site monitors measured air pollution exposure. We used multivariable logistic regression and estimated coefficients using generalized estimating equations. Interaction was assessed between pollutants and genes and associations in genotype-specific strata were presented. False discovery rate was used to adjust for multiple comparisons. RESULTS: There were 803 episodes of bronchitis with an incidence rate of 56 per 1000 child-months. We found significant gene-environment interaction between PAH and four SNPs (EPHX1, (rs2854461), STAT4 (rs16833215), XPC (rs2228001 and rs2733532)), which became non-significant after adjusting for multiple comparisons. PM2.5 interactions with two XPC SNPs (rs2228001 and rs2733532) remained significant after accounting for multiple comparisons and those with CC alleles had a more than doubling of odds, OR=2.65 (95% CI: 1.91, 3.69) and 2.72 (95% CI: 1.95, 3.78), respectively, per 25 μg/m(3) increase in exposure. CONCLUSION: The findings suggest that the DNA repair gene XPC may play an important role in the air pollution-induced pathogenesis of the inflammatory disease bronchitis.

• MeSH
• bronchiální astma epidemiologie   MeSH
• bronchitida * epidemiologie   imunologie   MeSH
• dítě MeSH
• genotyp MeSH
• incidence MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus MeSH
• látky znečišťující vzduch škodlivé účinky   analýza   MeSH
• lidé MeSH
• mladiství MeSH
• náhodné rozdělení MeSH
• oprava DNA genetika   MeSH
• pevné částice škodlivé účinky   analýza   MeSH
• polycyklické aromatické uhlovodíky škodlivé účinky   analýza   MeSH
• předškolní dítě MeSH
• přirozená imunita účinky léků   MeSH
• xenobiotika škodlivé účinky   analýza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• xenobiotika MeSH

The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

• Klíčová slova
• Brain imaging, Conference, Genetics, Gene–environment interaction, Meeting report, Schizophrenia, Treatment,
• MeSH
• interakce genů a prostředí * MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• mozek patologie   MeSH
• neurozobrazování MeSH
• schizofrenie * diagnóza   genetika   terapie   MeSH
• společnosti lékařské MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Itálie MeSH