A Genetic Population Isolate in The Netherlands Showing Extensive Haplotype Sharing and Long Regions of Homozygosity

Genetic isolated populations have features that may facilitate genetic analyses and can be leveraged to improve power of mapping genes to complex traits. Our aim was to test the extent to which a population with a former history of geographic isolation and religious endogamy, and currently with one of the highest fertility rates in The Netherlands, shows signs of genetic isolation. For this purpose, genome-wide genotype data was collected of 72 unrelated individuals from this population as well as in a sample of 104 random control subjects from The Netherlands. Additional reference data from different populations and population isolates was available through HapMap and the Human Genome Diversity Project. We performed a number of analyses to compare the genetic structure between these populations: we calculated the pairwise genetic distance between populations, examined the extent of identical-by-descent (IBD) sharing and estimated the effective population size. Genetic analysis of this population showed consistent patterns of a population isolate at all levels tested. We confirmed that this population is most closely related to the Dutch control subjects, and detected high levels of IBD sharing and runs of homozygosity at equal or even higher levels than observed in previously described population isolates. The effective population size of this population was estimated to be several orders of magnitude smaller than that of the Dutch control sample. We conclude that the geographic isolation of this population combined with rapid population growth has resulted in a genetic isolate with great potential value for future genetic studies

A Genetic Population Isolate in The Netherlands Showing Extensive Haplotype Sharing and Long Regions of Homozygosity.

Genetic isolated populations have features that may facilitate genetic analyses and can be leveraged to improve power of mapping genes to complex traits. Our aim was to test the extent to which a population with a former history of geographic isolation and religious endogamy, and currently with one of the highest fertility rates in The Netherlands, shows signs of genetic isolation. For this purpose, genome-wide genotype data was collected of 72 unrelated individuals from this population as well as in a sample of 104 random control subjects from The Netherlands. Additional reference data from different populations and population isolates was available through HapMap and the Human Genome Diversity Project. We performed a number of analyses to compare the genetic structure between these populations: we calculated the pairwise genetic distance between populations, examined the extent of identical-by-descent (IBD) sharing and estimated the effective population size. Genetic analysis of this population showed consistent patterns of a population isolate at all levels tested. We confirmed that this population is most closely related to the Dutch control subjects, and detected high levels of IBD sharing and runs of homozygosity at equal or even higher levels than observed in previously described population isolates. The effective population size of this population was estimated to be several orders of magnitude smaller than that of the Dutch control sample. We conclude that the geographic isolation of this population combined with rapid population growth has resulted in a genetic isolate with great potential value for future genetic studies

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology