External Jugular Vein Aneurysm Presenting as a Cervical Mass

Venous aneurysms are rare causes of neck mass. Among neck veins, aneurysms of the external jugular vein are extremely uncommon. We present a case of a woman with a history of prior internal jugular vein catheterization who presented at a rural primary health care unit with a nontender progressively enlarging swelling in the right supraclavicular region. B-mode and Doppler ultrasound examination revealed a saccular dilatation of the external jugular vein, suggesting a posttraumatic venous aneurysm. Saccular aneurysms of the external jugular vein are uncommon and only rarely lead to serious complications. Access to ultrasound examination can allow early detection of this entity

Attitudes to kidney donation among primary care patients in rural Crete, Greece

<p>Abstract</p> <p>Background</p> <p>In Greece, there is limited research on issues related to organ donation, and the low rate of registration as donors requires explanation. This study reports the findings of a survey of knowledge and attitudes to kidney donation among primary care patients in rural Crete, Greece.</p> <p>Methods</p> <p>Two rural primary care settings in the island of Crete, Anogia Health Centre and Vrachasi Practice, were involved in a questionnaire survey. This was conducted among primary care patients (aged 18 years and over) with routine appointments, to assess their knowledge and attitudes to kidney donation. General practitioners (GPs) recruited patients and questionnaires were completed following the patients' medical consultation. Pearson's chi square tests were used and crude odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in order to investigate into the possible associations between the respondents' knowledge, attitudes and specific concerns in relation to their socio-demographic features. Logistic regression analyses were used to examine differences by geographical location.</p> <p>Results</p> <p>The 224 (92.5%) of the 242 primary care attenders who were approached agreed to participate. Only 2.2% (5/224) of the respondents carried a donor card. Most participants (84.4%, 189/224) did not feel well informed about registering as a kidney donor. More than half of the respondents (54.3%, 121/223) were unwilling to register as a kidney donor and donate kidneys for transplant after death. Over a third of respondents (35.4%, 79/223) were not confident that medical teams would try as hard as possible to save the life of a person who has agreed to donate organs. People with a higher level of education were more likely to be willing to register as kidney donors [(OR: 3.3; 95% CI: 1.8–6.0), p < 0.001)] and to be less worried about their kidneys being removed after death [(OR: 0.3; 95% CI: 0.1–0.5), p < 0.001)] than those having a lower level of education.</p> <p>Conclusion</p> <p>Lack of knowledge and information regarding organ donation and negative attitudes related to registration as donors were the main findings of this study. Efforts should be based on targeting the attitudes to organ donation of individuals and population groups.</p

Whole-genome sequencing analysis of the cardiometabolic proteome.

The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome sequencing (WGS) in 1328 individuals. We discover 131 independent sequence variant associations (P < 7.45 × 10-11) across the allele frequency spectrum, all of which replicate in an independent cohort (n = 1605, 18.4x WGS). We identify for the first time replicating evidence for rare-variant cis-acting protein quantitative trait loci for five genes, involving both coding and noncoding variation. We construct and validate polygenic scores that explain up to 45% of protein level variation. We find causal links between protein levels and disease risk, identifying high-value biomarkers and drug development targets

Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases

The Transferability of Lipid-Associated Loci Across African, Asian and European Cohorts

Abstract: Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r = 0.23–0.28, p < 1.9 × 10−14). Overall, there is evidence of reproducibility for ~75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions

Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits.

The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10-8; APOC3 and triglyceride levels, P = 1.5 × 10-26), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10-8), indicating a role for this gene in lipid metabolism

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways