Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Essays in Financial Economics

This dissertation consists of three chapters discussing issues in the field of financial economics. The first two chapters are largely empirical; the third chapter is mainly theoretical. In the first chapter (co-authored with Andrew Meldrum and Wen Yan) we develop a model for pricing hypothetical financial instruments that have their pay-offs tied to the evolution of a country's gross domestic product (GDP) growth ('GDP-linked bonds'). We first develop a no-arbitrage pricing model for these bonds in line with those applied to other financial securities. Absent data on actual prices given lack of trading, we device an alternative empirical strategy for estimation of our model. This strategy entails inferring the risk profile of GDP from a second term-structure model, this time of 'zero-coupon' equities, which can be taken to the data. After estimating the prices of GDP-linked bonds we decompose them into their components (including GDP growth expectations and GDP risk premia) and study their time series and term structure dynamics. In the second chapter (co-authored with Matias Ossandon-Busch and Dennis Reinhardt) we study the effect of price dislocations in the market for foreign currency (FX) swaps, an important source of funding for banks, on cross-border bank lending. Armed with a detailed balance sheet level dataset for banks operating from the UK, we examine how ex-ante exposure to FX swap-based funding affects the reaction of banks cross-border positions in the face of the mentioned dislocations in pricing. We also explore the role of potential shielding factors, including banks' reliance on intra-group funding. In the third chapter I develop a theoretical macroeconomic model featuring shocks to the availability of FX funding for banks (`dollar shortage shocks') and central bank swap lines as a monetary policy tool. First, I show that dollar shortage shocks can have significant negative consequences for macroeconomic aggregates by affecting bank lending. Second, I show how the availability of central bank swap lines, through which the local central bank can access foreign currency, can attenuate the negative consequences of dollar shortage shocks on the macroeconomy. </p