Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10-04) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10-09). On chromosome 5p13 we found cis-eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10-11). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10-47). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10-09). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms

Evaluation of data repositories based on the FAIR Principles for IDCC 2017 practice paper

Corresponding data-set to IDCC 2017 Practice Paper 'Are the FAIR-Principles fair?'. Excel Spreadsheet with overview and categories, frequency and proportion statistics, and graphs of 37 data repositories in the Netherlands and Europe. Compliance Evaluation is based on the principles and facets of the FAIR principles; re3data.org is the source for the data repositories

Genetic interactions in nonsyndromic orofacial clefts in Europe - EUROCRAN study

Background: Nonsyndromic cleft lip with or without cleft palate (nsCL6P) and nonsyndromic cleft palate (nsCP) are caused by a combination of genetic and environmental risk factors. We investigated gene-environment and gene-gene joint effects in a large multicenter study of caseparent triads. Methods: The nsCL6P or nsCP triads were recruited in 11 European countries between 2001 and 2005. We collected DNA samples from infants and from their mothers and fathers, and mothers completed a questionnaire on exposures, including smoking and folic acid supplement use during pregnancy. We used log-linear regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between nsCL6P or nsCP and variants in MTHFR, MTHFD1, TGFA, SATB2, and MSX1, stratifying by environmental or genetic factors. Results: We obtained genotype and exposure data for 728 nsCL±P triads and 292 nsCP triads. In male infants, there was no association between the mother's homozygous MSX1 p(CA)4/4 genotype and nsCL±P (RR, 0.98; 95% CI, 0.63-1.54), but this maternal genotype resulted in a doubling of risk for female infants (RR, 2.21; 95% CI, 1.13-4.34). There was evidence suggestive of gene-gene joint-effects between MTHFR-TGFA for nsCP but not for nsCL±P. Conclusion: Although we chose the genes and their variants and putative joint effects based on associations previously reported in the literature, we replicated few associations. These results do not provide evidence supporting associations between these genes and oral clefts in European populations, although gene-environment and gene-gene interactions could play a role in oral cleft etiology

Beta-decay studies of nuclei far from stability near N=28

NESTER AC

The Role of Dietary Approach in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most frequent gastrointestinal diseases. In IBS multiple pathophysiological mechanisms including alterations in intestinal motility, permeability, nutrient absorption, and intestinal microbiota have been implicated. Foods are commonly reported by patients to be a trigger of symptoms and therefore are likely involved in the generation of symptoms in IBS. Among all possible therapeutic options, a first-line approach to IBS is dietary education and identification of foods potentially responsible for the onset or worsening of symptoms. Dietary approaches include reduction of gas-producing foods (i.e. fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)), lactose and gluten. Further studies are required to link the ultimate role of diets in different IBS subtypes

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary

Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies

Contains fulltext : 220009.pdf (Publisher’s version ) (Closed access)BACKGROUND: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. METHODS: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. RESULTS: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (r(g) = 0.13, P = 2 × 10(-04)) and a r(g) of 0.12 between WHR and BE/EA (P = 1 × 10(-02)). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (r(g) = 0.17, P = 1.2 × 10(-03)), and WHR and EA in males (r(g) = 0.18, P = 1.51 × 10(-02)). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10(-03)) and WHR and BE/EA risk variants (P = 2 × 10(-02)). CONCLUSIONS: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. IMPACT: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology

On the dynamics of liquids in their viscous regime approaching the glass transition

Recently, Mallamace et al. (Eur. Phys. J. E 34, 94 (2011)) proposed a crossover temperature, T × , and claimed that the dynamics of many supercooled liquids follow an Arrhenius-type temperature dependence between T × and the glass transition temperature T g . The opposite, namely super-Arrhenius behavior in this viscous regime, has been demonstrated repeatedly for molecular glass-former, for polymers, and for the majority of the exhaustively studied inorganic glasses of technological interest. Therefore, we subject the molecular systems of the Mallamace et al. study to a “residuals” analysis and include not only viscosity data but also the more precise data available from dielectric relaxation experiments over the same temperature range. Although many viscosity data sets are inconclusive due to their noise level, we find that Arrhenius behavior is not a general feature of viscosity in the T g to T × range. Moreover, the residuals of dielectric relaxation times with respect to an Arrhenius law clearly reveal systematic curvature consistent with super-Arrhenius behavior being an endemic feature of transport properties in this viscous regime. We also observe a common pattern of how dielectric relaxation times decouple slightly from viscosity