A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes