| 1. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 2. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 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
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 3. |
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| 4. |
- Dunn, R. J. H., et al.
(författare)
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GLOBAL CLIMATE : State of the Climate in 2020
- 2021
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Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 102:8
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Tidskriftsartikel (refereegranskat)
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| 5. |
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| 6. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Eijsbouts, C., et al.
(författare)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 8. |
- Ferreira, N., et al.
(författare)
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The impact of the coronavirus (COVID-19) pandemic on individuals with gastrointestinal disorders: A protocol of an international collaborative study
- 2021
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Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The COVID-19 pandemic has had a significant impact on mental health across the globe. People living with a chronic gastrointestinal (GI) disorder might be particularly at risk of mental health complications given higher rates of comorbid anxiety and depression compared to the healthy population. As GI disorders affect up to 40% of the population worldwide, this international collaborative study seeks to evaluate the extent of the impact of the COVID-19 pandemic on GI symptoms specifically and more generally on the well-being of those living with chronic GI conditions. Methods: A longitudinal survey with three time points (baseline, 6-month, and 12-month) will be conducted online. Adult participants with GI disorders from multiple countries will be recruited via patient associations, social media advertising, utilizing snowball sampling. Participants will be invited to complete a battery of questionnaires including demographic and health parameters, and measures of gastrointestinal symptoms, fear of COVID-19, perceived impact of COVID-19, illness perceptions, coping, depression, anxiety, stress, catastroph-izing, and quality of life, using validated measures where available. Statistical analyses will include univariate descriptive models, multivariate models utilizing regression, mediation, and moderation, and latent growth models. Conclusions: This project may present novel information to the field of psychogastroenterology and may provide crucial information regarding the areas of impact for individuals with GI disorders during and following the pandemic. Further, this information can guide healthcare providers and patient associations on how to target support related to the pandemic mental health sequelae for these patients.
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| 9. |
- Fritz, N., et al.
(författare)
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The serotonin receptor 3E variant is a risk factor for female IBS-D
- 2022
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Ingår i: Journal of Molecular Medicine-Jmm. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 100:11, s. 1617-1627
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.
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| 10. |
- Gorski, Mathias, et al.
(författare)
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1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.
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| 14. |
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| 15. |
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| 17. |
- Boeckxstaens, G. E., et al.
(författare)
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Phenotyping of subjects for large scale studies on patients with IBS
- 2016
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:8, s. 1134-1147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a ‘large’ pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd
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| 26. |
- Massy, ZA, et al.
(författare)
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Nephrology and Public Policy Committee propositions to stimulate research collaboration in adults and children in Europe
- 2019
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 34:9, s. 1469-1480
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Tidskriftsartikel (refereegranskat)abstract
- The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.
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| 27. |
- Mikocka-Walus, Antonina, et al.
(författare)
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Exploring the Relationship Between Self-Isolation and Distress Among People with Gastrointestinal Disorders During the COVID-19 Pandemic
- 2022
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Ingår i: Journal of clinical psychology in medical settings. - : Springer. - 1068-9583 .- 1573-3572. ; 29:3, s. 654-665
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to explore the association between perceived isolation and symptoms of distress in people with GI disorders at the time of the pandemic; and to examine factors which moderate this relationship. This online cross-sectional survey was advertised in May-September 2020 via patient organisations and associated social media. Overall, 831 people (82% female, mean age 49 years) from 27 countries participated. A significant relationship between social isolation and psychological distress was noted (r = .525, p < .001). GI symptoms moderated the association between isolation and distress (B = .047, t = 2.47, p = .015). Interventions targeting these factors may help to reduce distress in people with GI disorders at the time of major stressors such as the COVID-19 pandemic.
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| 28. |
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| 29. |
- Mohr, S., et al.
(författare)
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The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
- 2021
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Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 25:16, s. 8047-8061
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
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| 30. |
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| 31. |
- Ovaskainen, Otso, et al.
(författare)
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Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA
- 2024
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Ingår i: Scientific Data. - 2052-4463. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
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| 32. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 33. |
- Stengel, Gudrun, et al.
(författare)
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Ambivalent Incorporation of the Fluorescent Cytosine Analogues tC and tCo by Human DNA Polymerase alpha and Klenow Fragment
- 2009
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 48:31, s. 7547-7555
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Tidskriftsartikel (refereegranskat)abstract
- Westudied the incorporation of the fluorescent cytidine analogues 1,3-diaza-2-oxophenothiazine (tC) and 1,3-diaza-2-oxophenoxazine (tCo) by human DNA polymerase R and Klenow fragment of DNA polymerase I (Escherichia coli). These tricyclic nucleobases possess the regular hydrogen bonding interface of cytosine but are significantly expanded in size toward the major groove. Despite the size alteration, both DNA polymerases insert dtCTP and dtCoTP with remarkable catalytic efficiency. Polymerization opposite guanine is comparable to the insertion of dCTP, while the insertion opposite adenine is only ∼4-11 times less efficient than the formation of a T-A base pair. Both enzymes readily extend the formed tC(o)-G and tC(o)-A base pairs and can incorporate at least four consecutive nucleotide analogues. Consistent with these results, both DNA polymerases efficiently polymerize dGTP and dATP when tC and tCo are in the template strand. Klenow fragment inserts dGTP with a 4-9-fold higher probability than dATP, while polymerase R favors dGTP over dATP by a factor of 30-65. Overall, the properties of tC(o) as a templating base and as an incoming nucleotide are surprisingly symmetrical and may be universal for A and B family DNA polymerases. This finding suggests that the aptitude for ambivalent base pairing is a consequence of the electronic properties of tC(o). © 2009 American Chemical Society.
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