Instrumental variable method for the causal relationship between soluble receptor for advanced glycation end-products (sRAGE) and risk of pancreatic cancer

This thesis project is motivated by the potential problem of using observational data to draw inferences about a causal relationship in observational epidemiology research when controlled randomization is not applicable. Instrumental variable (IV) method is one of the statistical tools to overcome this problem. Mendelian randomization study uses genetic variants as IVs in genetic association study. In this thesis, the IV method, as well as standard logistic and linear regression models, is used to investigate the causal association between risk of pancreatic cancer and the circulating levels of soluble receptor for advanced glycation end-products (sRAGE). Higher levels of serum sRAGE were found to be associated with a lower risk of pancreatic cancer in a previous observational study (255 cases and 485 controls). However, such a novel association may be biased by unknown confounding factors. In a case-control study, we aimed to use the IV approach to confirm or refute this observation in a subset of study subjects for whom the genotyping data were available (178 cases and 177 controls). Two-stage IV method using generalized method of moments-structural mean models (GMM-SMM) was conducted and the relative risk (RR) was calculated. In the first stage analysis, we found that the single nucleotide polymorphism (SNP) rs2070600 of the receptor for advanced glycation end-products (AGER) gene meets all three general assumptions for a genetic IV in examining the causal association between sRAGE and risk of pancreatic cancer. The variant allele of SNP rs2070600 of the AGER gene was associated with lower levels of sRAGE, and it was neither associated with risk of pancreatic cancer, nor with the confounding factors. It was a potential strong IV (F statistic = 29.2). However, in the second stage analysis, the GMM-SMM model failed to converge due to non- concaveness probably because of the small sample size. Therefore, the IV analysis could not support the causality of the association between serum sRAGE levels and risk of pancreatic cancer. Nevertheless, these analyses suggest that rs2070600 was a potentially good genetic IV for testing the causality between the risk of pancreatic cancer and sRAGE levels. A larger sample size is required to conduct a credible IV analysis.^

Cyberbullying and school attachment: An analysis of the 2005-2006 U.S. health behavior in school-aged children (HBSC) study

Despite a lack of consistent research, the possible association between school attachment and cyberbullying suggests that targeting school attachment as a method of increasing help-seeking behaviors may be important in intervention strategies for cyberbullying. The present study sought to fill the gap in current literature by examining cyberbullying and school attachment in a nationally representative sample of U.S. adolescents, grades 6-10 (n=9,227). Results found that negative school attachment was significantly associated with greater odds of cyberbullying victimization (OR=4.71, p<0.001), perpetration (OR=2.95, p<0.001), and cyberbully-victim status (OR=3.38, p<0.001). After adjustment for confounding variables, cyberbullying victimization remained significant (OR=1.90, p=0.002). Overall, the present analyses suggest that higher negative school attachment may be associated with higher frequency of cyberbullying behaviors. These findings provide evidence for an association between school attachment and cyberbullying, and support considerations that improving school attachment may be a potential source of intervention against cyberbullying in an adolescent population.^