Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

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Treball presentat al concurs: Realisierungswettbewerb "Neugesstaltung Ernst-AbbePlatz"

Waveform inversion of crosshole georadar data: influence of source wavelet variability and the suitability of a single wavelet assumption

Waveform-based tomographic imaging of crosshole georadar data is a powerful method to investigate the shallow subsurface because of its ability to provide images of electrical properties in near-surface environments with unprecedented spatial resolution. A critical issue with waveform inversion is the a priori unknown source signal. Indeed, the estimation of the source pulse is notoriously difficult but essential for the effective application of this method. Here, we explore the viability and robustness of a recently proposed deconvolution-based procedure to estimate the source pulse during waveform inversion of crosshole georadar data, where changes in wavelet shape with location as a result of varying near-field conditions and differences in antenna coupling may be significant. Specifically, we examine whether a single, average estimated source current function can adequately represent the pulses radiated at all transmitter locations during a crosshole georadar survey, or whether a separate source wavelet estimation should be performed for each transmitter gather. Tests with synthetic and field data indicate that remarkably good tomographic reconstructions can be obtained using a single estimated source pulse when moderate to strong variability exists in the true source signal with antenna location. Only in the case of very strong variability in the true source pulse are tomographic reconstructions clearly improved by estimating a different source wavelet for each transmitter location.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

Spotlight Switzerland

Overview of the CATI surveys tradition in Switzerland, evolution of coverage of the landline and mobile phones and implications for survey strategies

El Comportament humà en situacions de crisi: resultats del projecte de recerca europeo BESECU

Les aportacions que es presenten en aquest llibre mostren els resultats de la investigació sobre el comportament humà en situacions d’emergència que s’ha dut a terme en el marc del projecte de recerca europeu BeSeCu. El projecte Be- SeCu —acrònim de Behaviour, Security and Culture (Comportament, Seguretat i Cultura)— forma part de la línia d’investigació i coneixement en matèria de seguretat del Setè Programa Marc de la Unió Europea. Concretament, el projecte es centra en una de les necessitats bàsiques establertes per la política europea en matèria de seguretat, com és la de conèixer en profunditat la realitat de les emergències a través de les persones que les han patit o dels professionals que hi treballen diàriament. Per assolir aquest objectiu, el projecte ha investigat les diferències i similituds del comportament humà en diferents situacions d’emergència i en diversos països europeus per tal de millorar els processos d’evacuació i protecció en aspectes com ara la comunicació, les indicacions i els procediments d’intervenció dels agents actuants. Les situacions d’emergències s’han investigat mitjançant dos actors clau, és a dir des de l’òptica de persones que han estat víctimes d’una situació d’emergència i des de l’òptica dels professionals dels serveis d’emergència. El grup principal d’estudi dels serveis d’emergència ha estat els cossos de bombers. La investigació del comportament humà, tant de víctimes com dels serveis d’emergència (cossos de bombers), s’ha centrat en cinc tipus diferents d’emergències: incendis d’habitatge, incendis en edificis públics, atemptats terroristes, terratrèmols i inundacions. El projecte estava format per un consorci d’institucions en què participaven un grup multidisciplinari de psicòlegs, sociòlegs, criminòlegs, enginyers i professionals de les emergències que treballen en escoles de bombers i policies, serveis d’emergència, centres de recerca i investigació i universitats de set països europeus: • Alemanya: Ernst-Moritz-Arndt Universität Greifswald, Department of Health and Prevention, Institute of Psychology (coordinació del projecte); • Alemanya: Hamburg Fire and Emergency Service Academy; • Espanya: Institut de Seguretat Pública de Catalunya, Unitat de Recerca de l’Escola de Policia i de l’Escola de Bombers; • Anglaterra: University of Greenwich, Fire Safety Engineering Group; • Itàlia: Università di Bologna, Gruppo di Ricerca in Psicologia dell’Emergenza; • República Txeca: Prague Psychiatric Centre; • Suècia: Man-Technology-Organisation; • Turquia: Association of Emergency Ambulance Physicians.

Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.