Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. © 2014

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

Instant Video Revisiting for Reflection: Extending the Learning of Children and Teachers

This article discusses how instant video revisiting (IVR) promotes reflective thinking for both teachers and children. IVR was used as a daily classroom experience with both the children and the teachers throughout one semester in two preschool classrooms with children 2.5 to 5 years old. The teachers used a digital video camera to generate data to help them understand the behavior of the children and revisit the children\u27s actions immediately, with the children using the video clips to extend their learning. Two classroom examples illustrate how IVR supports the children\u27s learning and the teacher\u27s reflection of this learning. The first example describes how IVR helped the children reflect on their actions and solve their own conflicts. The second example describes the use of IVR to scaffold the children\u27s idea of the middle of a story, thereby strengthening their own thought processes in relation to a story construction

Planning for emergent curriculum that aligns with the Next Generation Science Standards using the Cycle of Inquiry System

This presentation will illustrate the ways that the teacher practices within the Cycle of Inquiry system (COI) align with the practices of scientists recommended by the National Research Council and guide emergent inquiry with children that aligns with the Next Generation Science Standards (NGSS). The COI and NGSS are organized around constructivist principles for teaching, learning, and research

Planning for emergent curriculum that aligns with the Next Generation Science Standards using the Cycle of Inquiry System

This presentation will illustrate the ways that the teacher practices within the Cycle of Inquiry system (COI) align with the practices of scientists recommended by the National Research Council and guide emergent inquiry with children that aligns with the Next Generation Science Standards (NGSS). The COI and NGSS are organized around constructivist principles for teaching, learning, and research

Drawing to Learn: A Classroom Case Study

As early childhood educators of young children, we recognize that children draw what they know from cultural transmissions, moving through many developmental transitions with drawing. As children’s skills developed, a PreK/Kindergarten teacher in a university laboratory school classroom with 27 children was interested in studying ways children can use drawing to enhance their learning of critical concepts within the curriculum. This paper explores her teacher research, a case study using an action research approach guided by these questions: (1) How do young children use drawing during short and long-term projects? (2) What can teachers learn from close attention to children’s representation drawing? A Drawing to Learn protocol was developed to study children’s drawings of curriculum topics like the wind, affording opportunities to use drawing to express their understanding of motion and their theories of how something works. The teacher research was organized around the Cycle of Inquiry process typically used for curriculum planning in the classroom. The curriculum planning data (observation, interpretation, questions, reflections) informed teachers’ understanding of the meaning of children’s drawings and guided teachers as to how to proceed to inquire more deeply into meaning and discovery with children. The findings of this two-semester study indicate multiple purposes and strategies for using drawings in the learning process (predict, study functions of objects, revisit and reflect, and plan)