IgA Nephropathy Genetic Risk Score to Estimate the Prevalence of IgA Nephropathy in UK Biobank

Background: IgA nephropathy (IgAN) is the commonest glomerulonephritis worldwide. Its prevalence is difficult to estimate, as people with mild disease do not commonly receive a biopsy diagnosis. We aimed to generate an IgA nephropathy genetic risk score (IgAN-GRS) and estimate the proportion of people with hematuria who had IgAN in the UK Biobank (UKBB). Methods: We calculated an IgAN-GRS using 14 single-nucleotide polymorphisms (SNPs) drawn from the largest European Genome-Wide Association Study (GWAS) and validated the IgAN-GRS in 464 biopsy-proven IgAN European cases from the UK Glomerulonephritis DNA Bank (UKGDB) and in 379,767 Europeans in the UKBB. We used the mean of IgAN-GRS to calculate the proportion of potential IgAN in 14,181 with hematuria and other nonspecific renal phenotypes from 379,767 Europeans in the UKBB. Results: The IgAN-GRS was higher in the IgAN cohort (4.30; 95% confidence interval [95% CI: 4.23-4.38) than in controls (3.98; 3.97-3.98; P < 0.0001). The mean GRS in UKBB participants with hematuria (n = 12,858) was higher (4.04; 4.02-4.06) than UKBB controls (3.98; 3.97-3.98; P < 0.0001) and higher in those with hematuria, hypertension, and microalbuminuria (n = 1323) (4.07; 4.02-4.13) versus (3.98; 3.97-3.98; P = 0.0003). Using the difference in these means, we estimated that IgAN accounted for 19% of noncancer hematuria and 28% with hematuria, hypertension, and microalbuminuria in UKBB. Conclusions: We used an IgAN-GRS to estimate the prevalence of IgAN contributing to common phenotypes that are not always biopsied. The noninvasive use of polygenic risk in this setting may have further utility to identify likely etiology of nonspecific renal phenotypes in large population cohorts.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was done with the UK Biobank resource (application 9072). UK Glomerulonephritis DNA Bank cohort. Piotr Słowinski, was consulted on the means method and helped with the simulation estimates and calculation. KS is funded by an Nation Institute for Health and Research (NIHR) Academic Clinical Fellowship. SAS is supported by a Diabetes UK PhD studentship (17/0005757). RAO is supported by a Diabetes UK Harry Keen Fellowship (16/0005529) MNW is supported by the Wellcome Trust Institutional Support Fund (WT097835MF). The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Healthpublished version, accepted version, submitted versio

Leukocytospermia and sperm preparation - a flow cytometric study

Reprod Biol Endocrinol. 2009 Nov 19;7:12

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Etiology of preeclampsia: an update

Preeclampsia still ranks as one of obstetrics major problems. Clinicians typically encounter preeclampsia as maternal disease with variable degrees of fetal involvement. More and more the unique immunogenetic maternal - paternal relationship is appreciated, and as such also the specific ‘genetic conflict’ that is characteristic of haemochorial placentation. Factors influencing the unique maternal-fetal (paternal) interaction probably include the length and type of sexual relationship, the maternal (decidual natural killer cells) acceptation of the invading cytotrophoblast (paternal HLA-C), and seminal levels of transforming growth factor-b and probably other cytokines. The magnitude of the maternal response would be determined by factors including a maternal set of genes determining her characteristic inflammatory responsiveness, age, quality of her endothelium, obesity/ insulin resistance and probably a whole series of susceptibility genes amongst which the thrombophilias received a lot of attention in recent years.http://www.ncbi.nlm.nih.gov/pubmed/2121350

Modern management of preterm labour

Preterm birth is the leading cause of neonatal morbidity and mortality. Cervical insufficiency is not an all or nothing phenomenon but a continuous variable which can lead to preterm deliveries at different gestational ages. The relationship between shortened cervical length and spontaneous preterm birth is consistent in several studies. Shortened cervical length can be diagnosed by transvaginal ultrasonography and treated by transvaginal cervical cerclage (TCC). A nomenclature to the different stages of prevention, as primary, secondary and tertiary was suggested to facilitate comparison of studies. Apart from cervical cerclage, the most widely used tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal and maternal side effects. There is growing interest in calcium channel blockers which appear to be more effective than beta-sympathomimetic drugs and have few side-effects