Refine
Has Fulltext
- no (3)
Year of publication
- 2019 (3) (remove)
Document Type
- Article (3)
Language
- English (3)
Is part of the Bibliography
- yes (3)
Keywords
- Childhood traits and disorders (1)
- Consortium (1)
- Genetics (1)
- Longitudinal (1)
- bank filtration (1)
- groundwater (1)
- groundwater modelling (1)
- surface-water relations (1)
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.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Bank filtration (BF) is an established indirect water-treatment technology. The quality of water gained via BF depends on the subsurface capture zone, the mixing ratio (river water versus ambient groundwater), spatial and temporal distribution of subsurface travel times, and subsurface temperature patterns. Surface-water infiltration into the adjacent aquifer is determined by the local hydraulic gradient and riverbed permeability, which could be altered by natural clogging, scouring and artificial decolmation processes. The seasonal behaviour of a BF system in Germany, and its development during and about 6 months after decolmation (canal reconstruction), was observed with a long-term monitoring programme. To quantify the spatial and temporal variation in the BF system, a transient flow and heat transport model was implemented and two model scenarios, 'with' and 'without' canal reconstruction, were generated. Overall, the simulated water heads and temperatures matched those observed. Increased hydraulic connection between the canal and aquifer caused by the canal reconstruction led to an increase of similar to 23% in the already high share of BF water abstracted by the nearby waterworks. Subsurface travel-time distribution substantially shifted towards shorter travel times. Flow paths with travel times <200 days increased by similar to 10% and those with <300 days by 15%. Generally, the periodic temperature signal, and the summer and winter temperature extrema, increased and penetrated deeper into the aquifer. The joint hydrological and thermal effects caused by the canal reconstruction might increase the potential of biodegradable compounds to further penetrate into the aquifer, also by potentially affecting the redox zonation in the aquifer.