Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Taxation and Government Quality: The Size, the Shape, or Just Europe 300 Years Ago?

Based on historical research, focusing mainly on early-modern Europe, it is assumed that taxation functions as a booster of state capacity and Quality of Government (QoG). The presence of this relationship for modern-day developing states is however heavily contested. This paper analyzes the relationship in a sub-Saharan context. By using new taxation data, which disaggregates resource income from other types of taxation (drawn from African Economic Outlook [2010]) we can with greater specificity dissect the different effects of different types of taxation. Through a multivariate regression analysis the paper shows that taxation, and in particular direct and indirect taxation, as a share of GDP seems to be associated with higher levels of QoG, although this relationship is at times weak. Furthermore, the relative dependence on direct and, to an extent indirect, taxation, measured as its share of the total tax base is shown to be more consistently coupled with better QoG. Thus, the paper concludes, more research on the importance of both size and shape of the tax base is warranted and needed

Taxation and Turnout in Swedish Municipalities

The link between taxation and representation is considered foundational to the emergence of demo-cratic governance. Nevertheless, the empirical relationship between taxation and the extent to which citizens actually exert representation by turning out to vote remains virtually unexplored. Using along panel, from 1979 to 2018, drawn from a relatively difficult case, Swedish municipalities, I find that hikes in local tax rates are linked to increased municipal voter turnout. Accounting for a wide range of confounders, including turnout in concurrent parliamentary elections, these results indicate an important untapped explanation for differences in turnout, while offering a rare explicit test ofthe taxation-representation argument drawn from a mature democracy

Taxation and Government Quality

The question of what creates government quality, or good institutions, is one of the central puzzles in modern political science. This dissertation investigates a hitherto underexplored cause: taxation. Historical research on early modern Europe has demonstrated that the collection of government revenue, mainly in the form of domestic taxes, was a main driver of the construction of a strong and meritocratic bureaucracy, and increased popular calls for accountability and representation, both key components of good institutions and the concept of government quality. Although a burgeoning literature has begun drawing parallels between this historical tax-driven process and institution building in today’s world, there is still a dearth of systematic tests of the link. Through a series of empirical investigations, this dissertation seeks to fill this gap. The introductory chapter presents global-level cross-country evidence that countries that impose higher taxes are also better governed. Through statistical analysis it furthermore finds a causal element present – taxation causes government quality, especially over the long run. The long-term nature inherent to this tax-driven process is further emphasized in paper I, which links present day government quality in former British colonies to the extent to which the colonial power collected revenue during the beginning of the 20th century. Paper II focuses on conditions further back in time, comparing religious financing in northwestern Europe during the early modern era and the Ottoman Empire. In the former setting, religious institutions were mainly financed and organized from below, leading to a strong tradition of local level accountability. In the latter such activities tended to be provided for, and accordingly controlled by, wealthy patrons. The study concludes that such variation in the way these essential public services were run can be tied to the subsequent divergence in level of democracy and openness in the Arab and western European countries. Paper III investigates a crucial mechanism inherent to the taxation-government quality hypothesis, namely the idea that taxation activates citizens to take political action. By analyzing individuals’ taxpaying behavior in sub-Saharan Africa, the study finds that people who pay taxes are more politically interested than those who do not pay. Finally, paper IV returns to the present day context. It poses the argument that the generally positive relationship between taxation and government quality in large part is driven by democratic states. Through analysis on global cross-country data, as well as data on individuals in sub-Saharan African, this hypothesis is supported. In sum, the findings in this dissertation support the notion of placing taxation more centrally in the ongoing discussion of how government quality and good institutions are created

The electoral consequences of institutional failure: A comparative study of audits, rulers, and voters in Swedish municipalities

Electoral accountability is widely considered an essential element for ascertaining institutional quality. Nevertheless, and contrary to this notion, a growing body of empirical research finds weak or limited support for the notion that voters actually punish political corruption, a central but partial aspect of institutional quality. Instead, I introduce the concept of institutional performance voting, capturing institutional quality as a whole. Using a novel dataset on performance audit reports in Swedish municipalities, I find that voters punish mayoral parties responsible for institutional dysfunction

Procurement and Competition in Swedish Municipalities.

This paper asks if low political competition is associated with manipulation of public procurement pro-cesses. Using unique Swedish municipal data from 2009 to 2015, it demonstrates that when one party dominates local politics, procurement quality decreases and corruption risks increase. Most striking is that the risk for getting only one bid on what is intended to be an open tender considerably increases with longstanding one-party-rule. Findings suggest that entrenched parties are able to exert favoritistic control over public procurement due to less well-functioning internal and external control mechanisms: bureau-cratic human capital decreases, municipal audits are more prone to be controlled by the ruling majority, and politicians are less susceptible to media pressure. These results are particularly interesting from a comparative perspective since Sweden, being an old democracy with a meritocratic bureaucracy, low levels of corruption and clientelism is an unlikely case in which to find these tendencies

Marketization and the Quality of Residential Elderly Care in Sweden

Against a backdrop of increased levels of marketization of welfare services in OECD countries, this article aims to shed light on the separate effects of private ownership and competition on service quality. Using residential elderly care in Sweden as our case, we leverage unique panel data of ownership and competition against a set of indicators, pertaining to the structure, process and outcome dimensions of care quality. The main finding of our analyses is that competition does surprisingly little for quality: private entrepreneurs perform neither better nor worse under stiff competition and the quality of care is approximately the same in those nursing homes that are exposed to competition from private actors as in those that are not