Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Innovative models of pension fund governance in the context of the global financial crisis.

The global financial crisis has posed profound threats to pension welfare worldwide. This is particularly so in the United Kingdom with the closure of private defined benefit plans, and the heavy losses experienced by many defined contribution pension plan participants. Meeting these challenges has placed a premium on plan governance, given its link to fund performance. This paper begins by considering the academic literature on institutional change, including an analysis of the most common ways of responding to a changing environment. It is noted that the nature and scope of institutional response to a changing environment depends, in part, upon funds’ governance budgets, including time, expertise and common commitment. Our research on UK governance suggests that incremental adaptation has been the operative strategy augmented, in some cases, by the adoption of UK corporate governance practices. Three types of innovation in the governance of UK pension plans are identified: the transformation of decision-making, the pension buy-out and fiduciary management alongwith an emerging ‘new’ model of pension fund governance. In the penultimate section of this paper, lessons from UK best practice are drawn for institutions that face unprecedented challenges in realising the pension promise. Thereafter, we suggest a possible approach for regulators to strengthen the pension fund sector, based on improved disclosure, independent board chairs and the skills of board members

DC Pension Fund Best-practice Design and Governance.

The design and governance of pension funds is an important topic of academic research and public policy and has significant implications for the welfare of participants. Here we focus upon the design and governance of defined contribution (DC) pension plans which have become the de facto model of occupational pensions in most countries. The study synthesises the findings of a year-long research project based upon in-depth interviews with the sponsors and managers of leading schemes from around the world. We begin with the dual nature of the governance problem characteristic of DC pension plans, emphasising aspects related to the self-governance of individuals in relation to their long-term interests as well as the ambivalence and conflicts of interest in plan sponsors. With those problems in mind, we focus on the design of DC pension plans and then their governance so as to challenge existing institutions in particular jurisdictions. Our findings have implications for employer-sponsored plans, multi-employer plans, and the public utilities that have been established or proposed that may transcend company-based and industry-based pension institutions. Whereas DC plans were once believed to be simple solutions to burdensome defined benefit liabilities, it is shown that there is nothing simple about a well-designed DC pension plan. In essence, the complexities associated with DB liabilities have been exchanged for complexities in the design and management of DC institutions

DC Pension Fund Best-practice Design and Governance.

The design and governance of pension funds is an important topic of academic research and public policy and has significant implications for the welfare of participants. Here we focus upon the design and governance of defined contribution (DC) pension plans which have become the de facto model of occupational pensions in most countries. The study synthesises the findings of a year-long research project based upon in-depth interviews with the sponsors and managers of leading schemes from around the world. We begin with the dual nature of the governance problem characteristic of DC pension plans, emphasising aspects related to the self-governance of individuals in relation to their long-term interests as well as the ambivalence and conflicts of interest in plan sponsors. With those problems in mind, we focus on the design of DC pension plans and then their governance so as to challenge existing institutions in particular jurisdictions. Our findings have implications for employer-sponsored plans, multi-employer plans, and the public utilities that have been established or proposed that may transcend company-based and industry-based pension institutions. Whereas DC plans were once believed to be simple solutions to burdensome defined benefit liabilities, it is shown that there is nothing simple about a well-designed DC pension plan. In essence, the complexities associated with DB liabilities have been exchanged for complexities in the design and management of DC institutions