| 1. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Eckardt, Johanna, et al.
(författare)
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Comparison of the consumers’ expected and actual perception of food investigated by Napping : a case study with Béarnaise sauce
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the present work we investigate the consumers’ expected perception of food, using packages of béarnaise sauce, with the preference of the actual product. Further we compare the results of the consumer panel with the outcome of an analytical sensory panel. The ambition was also to use innovative techniques to get additional insights of the consumers’ perception of food. Global Napping was performed with a consumer panel on the expected preference and partial Napping was conducted for evaluating the perception of the actual products. Results were complemented with preference tests and rankings, as well as the connection of the product to a package. An analytical sensory panel performed partial Napping of the products. In addition new and simple method of Napping data evaluation is presented. The results showed a mismatch between the perception of the package and the actual product. Different groups, here named as "emotional" and "rational", perceived products in diverse ways. The consumer panel was a highly inhomogeneous group of individuals, whereby the sensory analytical panel had high agreement. Consumers, who used to buy a certain product could not necessarily distinguish this product, neither did they rate this product as their first choice.
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| 3. |
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| 4. |
- Eckardt, Johanna, 1984, et al.
(författare)
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Comparison of the consumers expected and actual perception of food investigated by napping: a case study with béarnaise sauce
- 2013
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Ingår i: ESN at the 10th Pangborn Sensory Science Symposium, 11-15th August, 2013 Rio De Janeiro, Brazil.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study was to investigate consumers’ expected and actual perception of food, using packages of béarnaise sauce and actual products. In total six packages of béarnaise sauce were evaluated, whereas seven products were presented, including one tested twice. A naïve consumer panel of 15 assessors, 8 female and 7 male, with children living at home were recruited and selected by their preferences and buying patterns of béarnaise sauce, as well as their anticipated emotional and rational personality. The results of the consumer panel were compared with those of an analytical sensory panel.A further goal was to use innovative techniques to gain additional insight on the consumers’ perception of food. Global Napping was performed with the consumer panel on their expected preferences and partial Napping was conducted to evaluate their perceptions of the actual products. The Napping data were complemented with preference tests and rankings. The consumers were also asked to connect the tasted products to the packages. An analytical sensory panel performed partial Napping of the products. A new evaluation method of the resulting Napping data was introduced using Euclidian distances on individual tablecloths, which enable a much more user-friendly interpretation of the data.The results showed that there is a large difference between consumers’ expected and actual perceptions of the package and the actual product. Data also indicate that the more rational thinking consumers were less manipulated or influenced compared to the emotional ones. The analytical sensory panel was a group of high agreement and homogeneity, while the consumer panel showed great differences in their experiences of the packages as well as the products. Consumers who usually bought a certain product could not necessarily distinguish it from the other options; neither did they rate it as their first choice.
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| 5. |
- Eckardt, Johanna, et al.
(författare)
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Long-term frozen storage of wheat bread and dough : Effect of time, temperature and fibre on sensory quality, microstructure and state of water
- 2013
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Ingår i: Journal of Cereal Science. - : Elsevier BV. - 0733-5210 .- 1095-9963. ; 57:1, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine effect of storage time, storage temperature and addition of fibre on sensory quality, state of water, microstructure and texture of bread and dough. Samples with and without fibre, were stored frozen for 2, 3.5 and 6 months at temperatures of -19, -16 and -8 °C as dough and bread. Sensory quality was evaluated by a trained analytical panel. Microstructure was analysed by light microscopy. Texture measurements were performed on bread, and the state of water was measured by differential scanning calorimetry. Bread without fibre stored as dough at -19 °C was the sample most like freshly baked bread. Sensory evaluation also confirmed that quality of the final bread was improved if samples were stored as dough compared to stored as bread. The microstructure had larger gaps between the starch and gluten phases when stored at warmer temperatures, due to retrogradation of starch, dehydration of gluten and water migration. DSC measurements showed that bread stored at -19 °C gained extra amount of freezable water, but lost ice after storage at -8 °C. Texture measurements showed that firmness increased with extended storage time. Bread stored at -8 °C had lowest quality in all measurements.
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| 6. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 7. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 8. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 9. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 10. |
- Schlosser, Pascal, et al.
(författare)
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Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine
- 2023
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Ingår i: Nature Genetics. - 1546-1718. ; 55:6, s. 995-1008
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Tidskriftsartikel (refereegranskat)abstract
- The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite-disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments.
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