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.^

Effect of Certified Organic Products on Soybean Aphid

The soybean aphid (Aphis glycines), native to China, has become the most economically damaging insect in soybeans in northeast Iowa. Soybean aphid may have up to 18 generations per year, beginning with overwintering eggs on the alternate host buckthorn. In spring, winged aphids migrate from buckthorn to nearby emerged soybeans. Generations advance in these fields, and then another winged migration occurs in summer spreading from these fields to others. A third migration occurs in fall with aphids moving back to buckthorn. Depending on the season, soybean proximity to buckthorn, and soybean aphid migration patterns, populations of aphids tend to peak in soybeans anywhere from late July to early September. With higher aphid populations, the production of honeydew (the excrement of the aphid) and the resulting black fungus that grows on it (sooty mold) may become apparent. Aphid feeding may cause stunted plants, reduced pods and seeds, and may also transmit viruses that could cause mottling and distortion of leaves, reduced seed set, and discolored seeds.