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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.
River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth’s biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented “next-generation biomonitoring” by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Moving in the Anthropocene
(2018)
Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.
Standing crop and species composition in semiarid grassland are linked to long-term patterns of water availability, but grasslands are characterized by large single-season variability in rainfall. We tested whether a single season of altered water availability influenced the proportions of grasses and shrubs in a semiarid grassland near the northern edge of the North American Great Plains. We studied stands of the clonal shrub snowberry (Symphoricarpos occidentalis) and adjacent grassland dominated by the native grasses Stipa spartea and Bouteloua gracilis. Rain was excluded and water supplied in amounts corresponding to years of low, medium, and high rainfall, producing a 2 - 4-fold range in monthly precipitation among water supply treatments. There were ten replicate plots of each water treatment in both snowberry stands and grassland. Grass standing crop increased significantly with water availability in grassland but not inside snowberry stands. Total standing crop and shrub stem density increased significantly with water supply, averaged across both communities. In contrast, water had no effect on shrub standing crop or light penetration. In summary, our finding that water has significant effects on a subset of components of grassland vegetation is consistent with long-term, correlational studies, but we also found that a single season of altered water supply had no effect on other important aspects of the ecosystem.
Variation in nitrogen deposition and available soil nitrogen in a forest–grassland ecotone in Canada
(2004)
Regional variation in nitrogen (N) deposition increases plant productivity and decreases species diversity, but landscape- or local-scale influences on N deposition are less well-known. Using ion-exchange resin, we measured variation of N deposition and soil N availability within Elk Island National Park in the ecotone between grassland and boreal forest in western Canada. The park receives regionally high amounts of atmospheric N deposition (22 kg ha⁻¹ yr⁻¹). N deposition was on average higher ton clayrich luvisols than on brunisols, and areas burned 1 – 15 years previously received more atmospheric N than unburned sites. We suggest that the effects of previous fires and soil type on deposition rate act through differences in canopy structure. The magnitude of these effects varied with the presence of ungulate grazers (bison, moose, elk) and vegetation type (forest, shrubland, grassland). Available soil N (ammonium and nitrate) was higher in burned than unburned sites in the absence of grazing, suggesting an effect of deposition. On grazed sites, differences between fire treatments were small, presumably because the removal of biomass by grazers reduced the effect of fire. Aspen invades native grassland in this region, and our results suggest that fire without grazing might reinforce the expansion of forest into grassland facilitated by N deposition.
Regional variation in nitrogen (N) deposition increases plant productivity and decreases species diversity, but landscape- or local -scale influences on N deposition are less well-known. Using ion-exchange resin, we measured variation of N deposition and soil N availability within Elk Island National Park in the ecotone between grassland and boreal forest in western Canada. The park receives regionally high amounts of atmospheric N deposition (22 kg ha(-1) yr(- 1)). N deposition was on average higher ton clay-rich luvisols than on brunisols, and areas burned 1-15 years previously received more atmospheric N than unburned sites. We suggest that the effects of previous fires and soil type on deposition rate act through differences in canopy structure. The magnitude of these effects varied with the presence of ungulate grazers (bison, moose, elk) and vegetation type (forest, shrubland, grassland). Available soil N (ammonium and nitrate) was higher in burned than unburned sites in the absence of grazing, suggesting an effect of deposition. On grazed sites, differences between fire treatments were small, presumably because the removal of biomass by grazers reduced the effect of fire. Aspen invades native grassland in this region, and our results suggest that fire without grazing might reinforce the expansion of forest into grassland facilitated by N deposition
1 Atmospheric nitrogen (N) deposition has become one of the most important agents of vegetation change in densely populated regions, It may also contribute to forest expansion into grasslands at the northern edge of the North American Great Plains. 2 We measured N deposition and available soil N with ion-exchange resin over 2 years in six national parks in areas varying in population density and industrialization. N deposition was significantly higher in four parks in densely populated regions than in two remote parks. 3 Available soil N increased significantly with N deposition across all parks. 4 We measured N mass and N-15 abundance (delta N-15) in vegetation and soil in two parks: Elk Island, receiving 22 kg N ha(-1) year(-1), and Jasper, receiving 8 kg N ha(-1) year(-1). Differences between parks in tissue N concentrations were small, but forest expansion over five decades resulted in the mass of N in vegetation increasing by 74% in Elk Island but by only 26% in Jasper. delta N-15 in forest vegetation was significantly lower in Elk Island than in Jasper, suggesting that anthropogenic sources contribute significantly to the high rates of N entering that ecosystem. 5 We determined the rate of forest expansion within parks using six decades of aerial photographs, Parks in aspen parkland and boreal forest showed a strong positive relationship between forest expansion and N deposition. The relationships found between N deposition, available soil N and forest expansion suggest that even comparatively low rates of N deposition may accelerate the expansion of forest into temperate grasslands.