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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Agricultural soils have a high potential for sequestration of atmospheric carbon due to their volume and several promising management options. However, there is a remarkable lack of information about the status quo of organic carbon in agricultural soils. In this study a comprehensive data set of 384 cropland soils and 333 grassland soils within the state of Bavaria in southeast Germany was analyzed in order to provide representative information on total amount, regional distribution and driving parameters of soil organic carbon (SOC) and nitrogen (N) in agricultural soils of central Europe. The results showed that grassland soils stored higher amounts of SOC (11.8 kg m(-2)) and N (0.92 kg m(-2)) than cropland soils (9.0 and 0.66 kg m(-2), respectively) due to moisture-induced accumulation of soil organic matter (SOM) in B horizons. Surprisingly, no distinct differences were found for the A horizons since tillage led to a relocation of SOM with depth in cropland soils. Statistical analyses of driving factors for SOM storage revealed soil moisture, represented by the topographic wetness index (TWI), as the most important parameter for both cropland and grassland soils. Climate effects (mean annual temperature and precipitation) were of minor importance in agricultural soils because management options counteracted them to a certain extent, particularly in cropland soils. The distribution of SOC and N stocks within Bavaria based on agricultural regions confirmed the importance of soil moisture since the highest cropland SOC and N stocks were found for tertiary hills and loess regions, which exhibited large areas with potentially high soil moisture content in extant floodplains. Grassland soils showed the highest accumulation of SOC and N in the Alps and Pre-Alps as a result of low temperatures, high amounts of precipitation and high soil moisture content in areas of glacial denudation. Soil class was identified as a further driving parameter for SOC and N storage in cropland soils. In total, cropland and grassland soils in Bavaria store 242 and 134 Mt SOC as well as 19 and 12 Mt N down to a soil depth of 1 m or the parent material, respectively.
Temperate forest soils of central Europe are regarded as important pools for soil organic carbon (SOC) and thought to have a high potential for carbon (C) sequestration. However, comprehensive data on total SOC storage, particularly under different forest types, and its drivers is limited. In this study, we analyzed a forest data set of 596 completely sampled soil profiles down to the parent material or to a depth of 1 m within Bavaria in southeast Germany in order to determine representative SOC stocks under different forest types in central Europe and the impact of different environmental parameters. We calculated a total median SOC stock of 9.8 kg m(-2) which is considerably lower compared with many other inventories within central Europe that used modelled instead of measured soil properties. Statistical analyses revealed climate as controlling parameter for the storage of SOC with increasing stocks in cool, humid mountainous regions and a strong decrease in areas with higher temperatures. No significant differences of total SOC storage were found between broadleaf, coniferous and mixed forests. However, coniferous forests stored around 35% of total SOC in the labile organic layer that is prone to human disturbance, forest fires and rising temperatures. In contrast, mixed and broadleaf forests stored the major part of SOC in the mineral soil. Moreover, these two forest types showed unchanged or even slightly increased mineral SOC stocks with higher temperatures, whereas SOC stocks in mineral soils under coniferous forest were distinctly lower. We conclude that mixed and broadleaf forests are more advantageous for C sequestration than coniferous forests. An intensified incorporation of broadleaf species in extent coniferous forests of Bavaria would prevent substantial SOC losses as a result of rising temperatures in the course of climate change.
Carbon storage capacity of semi-arid grassland soils and sequestration potentials in northern China
(2015)
Organic carbon (OC) sequestration in degraded semi-arid environments by improved soil management is assumed to contribute substantially to climate change mitigation. However, information about the soil organic carbon (SOC) sequestration potential in steppe soils and their current saturation status remains unknown. In this study, we estimated the OC storage capacity of semi-arid grassland soils on the basis of remote, natural steppe fragments in northern China. Based on the maximum OC saturation of silt and clay particles <20m, OC sequestration potentials of degraded steppe soils (grazing land, arable land, eroded areas) were estimated. The analysis of natural grassland soils revealed a strong linear regression between the proportion of the fine fraction and its OC content, confirming the importance of silt and clay particles for OC stabilization in steppe soils. This relationship was similar to derived regressions in temperate and tropical soils but on a lower level, probably due to a lower C input and different clay mineralogy. In relation to the estimated OC storage capacity, degraded steppe soils showed a high OC saturation of 78-85% despite massive SOC losses due to unsustainable land use. As a result, the potential of degraded grassland soils to sequester additional OC was generally low. This can be related to a relatively high contribution of labile SOC, which is preferentially lost in the course of soil degradation. Moreover, wind erosion leads to substantial loss of silt and clay particles and consequently results in a direct loss of the ability to stabilize additional OC. Our findings indicate that the SOC loss in semi-arid environments induced by intensive land use is largely irreversible. Observed SOC increases after improved land management mainly result in an accumulation of labile SOC prone to land use/climate changes and therefore cannot be regarded as contribution to long-term OC sequestration.
Using novel longitudinal data, this paper studies the short- and medium-term effects of Russia's invasion of Ukraine on February 24, 2022 on social trust of adolescents in Germany. Comparing adolescents who responded to our survey shortly before the start of the war with those who responded shortly after the conflict began and applying difference-in-differences (DiD) models over time, we find a significant decline in the outcome after the war started. These findings provide new evidence on how armed conflicts influence social trust and well-being among young people in a country not directly involved in the war.
Using novel longitudinal data, this paper studies the short- and medium-term effects of Russia's invasion of Ukraine on February 24, 2022 on social trust of adolescents in Germany. Comparing adolescents who responded to our survey shortly before the start of the war with those who responded shortly after the conflict began and applying difference-in-differences (DiD) models over time, we find a significant decline in the outcome after the war started. These findings provide new evidence on how armed conflicts influence social trust and well-being among young people in a country not directly involved in the war.
Portal Transfer 2024
(2024)
Liebe Leserinnen und Leser, die eigene „Blase“ verlassen, Perspektiven wechseln, Silo-Mentalität überwinden – was der Wissenschaft in ihrem Innern gelingt, ja gelingen muss, um erfolgreich zu sein, stellt sie in ihrer Außenwirkung noch immer vor Herausforderungen. Dabei gehört es doch inzwischen zum Selbstverständnis moderner Universitäten, öffentlich zu erklären, woran in ihren Räumen geforscht wird, sich in gesellschaftliche Diskurse einzubringen und ihre Erkenntnisse zügig in die Praxis zu überführen.
Die Universität Potsdam hat diese Transferaufgaben neben Lehre und Forschung als dritte Säule installiert und ihrem Gebäude damit noch mehr Stabilität verliehen. Seit Jahren gehört sie im nationalen Vergleich zu den erfolgreichsten Hochschulen, wenn es darum geht, Start-ups zu fördern und aus der Forschung heraus Unternehmen zu gründen: In diesem Magazin berichten wir von der Potassco Solutions GmbH des Informatikers Torsten Schaub, der mit seinem KI-System Clingo komplexe Optimierungsprobleme in Betrieben löst. Oder von der SEQSTANT GmbH, die mit innovativer Diagnostik Erreger von Atemwegserkrankungen in Echtzeit bestimmen kann. Wir zeigen aber auch, wie Forschungsteams mit der Industrie kooperieren, zum Beispiel mit der K-UTEC im thüringischen Sondershausen, um mit wissenschaftlichem Knowhow dazu beizutragen, dass dort in Produktionsabfällen kein wertvolles Lithium verloren geht.
Richtet sich der Technologietransfer vor allem an die Wirtschaft, so hilft der Wissenstransfer der gesamten Gesellschaft. Besonders stark ist die Universität Potsdam hier in der Bildung, denn mit ihren Lehramtsabsolventen schickt sie auch gleich den aktuellen Stand der Unterrichtsforschung in die Schulpraxis. Immer häufiger zieht dabei die Digitalisierung in die Klassenzimmer ein. Wie das gut gelingen kann, ist in diesem Magazin zu lesen. Zudem erklären wir, was die Sportwissenschaft zur Therapie von Depressionen beitragen kann oder wie die Umweltforschung das Risikomanagement in von Hochwasser bedrohten Regionen verbessern will. Ob in öffentlichen Verwaltungen oder politischen Institutionen – überall ist wissenschaftliche Expertise gefragt. Wir zeigen das am Beispiel von Frauke Brosius-Gersdorf, die als Juristin die Bundesregierung zur Regulierung des Schwangerschaftsabbruchs berät.
Der kürzeste Weg des Wissens aus der Universität in die Praxis führt zweifelsohne über die Alumni, die als Fach- und Führungskräfte im Land und darüber hinaus wirksam werden. Dass dieser Weg schon während des Studiums beginnen kann, beweisen die vielen studentischen Initiativen, die hier zu Wort kommen. Sie alle scheuen nicht das Rampenlicht: ob bei Science Slams auf den Bühnen im Land Brandenburg, bei den TEDx-Talks im Hans Otto Theater, beim Kunst-Rundgang in der Potsdamer Waschhaus-Arena oder mit englischsprachigem Schauspiel an der Uni. Öffentlich in Erscheinung treten, neue Formen finden, um Wissen in die Breite der Bevölkerung zu tragen – auch das gehört zum Transfer. Genau wie dieses Magazin.
Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.