A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Dying Safely

The burden of deaths due to noncommunicable disease, particularly in the elderly, is projected to rise from 59% in 2002 to 69% in 2030. The ageing population has increased the use of medical technology and life support systems for the support of elderly complex cases—the so-called “sick elderly.” Public expectations believe modern medicine and its associated miracles can prolong life almost indefinitely. Sophisticated technology and the way media portrays the latest miracles generates unrealistic expectations by relatives and often causes potential conflict at the end of life (EoL). The medicalization of death and dying, despite its inevitability has contributed to the disappearance of the concept of a dignified natural death. Dying and death are seen as the ultimate challenge for successful ageing or as a failure of medicine if doctors cannot offer hope of recovery. Unfortunately, in many terminal cases, efforts are made to prolong life under pressure from families as well as the culture of acute hospitals and their concentration on “curing.” Clinicians are often reluctant to recommend limitations of treatment and instead, often administer inappropriate treatment in the face of futility. This chapter is not about assisted dying, euthanasia, nor about the “right to die.” It is about recognition of dying by clinicians; acceptance of death as a natural part of the cycle of life; understanding what constitutes a “good death”; considering the ethical aspects of futile interventions; and reviewing best practice in providing quality of EoL. We discuss the role of doctors, nurses, and the health system in supporting patients and family through the transition

Improving study success and diversity in Dutch higher education using performance agreements

More and more governments have started to introduce elements of performance in the funding mechanisms for their higher education institutions. An example is a performance agreement: a contract signed between the funding authority and an individual higher education provider. In the Netherlands, a policy experiment involving performance agreements was concluded in 2016. We analyse whether the agreements actually have helped achieve the goals of improving student completion rates, educational quality and increasing the diversity in educational offerings. We present some indicators relating to these goals and discuss what can be learned from the performance agreements experiment in the Netherlands