31. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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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. |
- 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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34. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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35. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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36. |
- Schmidt Burg, Helena, 1992, et al.
(författare)
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Litteraturöversikter med AI: En pedagogisk resa för studenter, lärare och bibliotekarier
- 2023
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Ingår i: Nätverksträffen för Forskningsbibliotekens pedagogiska roll.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Vad händer när studenterna inte själva söker upp, väljer ut och sammanfattar litteratur utan istället låter en AI-tjänst göra det? Vilken kunskap behöver studenterna ha för att åstadkomma goda och tillförlitliga sammanfattningar och tolkningar av litteraturen med hjälp av AI-baserade tjänster? Vilken blir vår roll som bibliotekarier i processen och hur kan vi bäst stötta studenterna i en etisk användning av tjänsterna? Vad innebär förändringarna för vad vår undervisning ska innehålla och hur den ska planeras? Kom och utforska dessa frågor i en workshop där vi testar och diskuterar olika AI-verktyg tillsammans.
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37. |
- Schmidt Burg, Helena, 1992, et al.
(författare)
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Litteraturöversikter med AI: En pedagogisk resa för studenter och lärare
- 2023
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Ingår i: Högskolepedagogisk konferens i Göteborg (HKG 2023).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Debatten kring hur högre utbildning ska förhålla sig till olika tjänster som baseras på generativ AI har tagit fart sen lanseringen av ChatGPT i november 2022. Inte minst uppmärksammad är problematiken med att avgöra om texter speglar studentens lärande av det som ska examineras (t.ex. Linderoth, 2023; Weber-Wulff et al. 2023). En vanlig examinationsuppgift är att skriva någon form av litteraturöversikt, en uppgift som ofta innefattar att söka fram, välja ut och sammanfatta vetenskaplig litteratur och att utifrån denna genomföra en egen analys eller tolkning. Detta är en uppgift som AI-baserade tjänster blir allt bättre på att utföra, inklusive att föreslå referenser för att backa upp påståenden i texten. I förlängningen leder detta till att vi behöver fundera på vad som lärs vid användning av AI-tjänster jämfört med mer traditionella metoder för litteraturöversikter. Vad händer när studenterna inte själva söker upp, väljer ut och sammanfattar, utan istället låter en AI-tjänst göra det? Vilken kunskap behöver studenterna ha för att åstadkomma goda och tillförlitliga sammanfattningar och tolkningar av litteraturen med hjälp av AI-baserade tjänster? Vilka är våra roller som lärare och som bibliotekarier i processen? Workshoppen fokuserar på att prova att skapa en litteraturöversikt med stöd av någon AI-baserad tjänst och att diskutera erfarenheter av resultaten. Exempel hämtas från deltagarnas egna områden och erfarenheter. Workshoppens genomförande 1. Inledning samt kort presentation av ett urval AI-tjänster 2. Deltagarna testar verktygen och skapar begränsade litteraturöversikter med hjälp av en eller flera AI-tjänster. 3. Resultaten som genererats av de olika AI-tjänsterna jämförs med varandra och en diskussion förs kring implikationerna av att studenterna använder tjänsterna i utbildningen. Workshoppen riktar sig till - universitetslärare som hanterar någon form av uppgift som inkluderar litteraturöversikter - universitetslärare som är intresserade av de förändringar som AI-baserade tekniker får för högre utbildning - undervisande bibliotekarier Referenser Linderoth, J. (2023-06-08). Varför vi inte längre kan ha skrivna hemuppgifter i högre utbildning. YouTube.com https://www.youtube.com/watch?v=GZOSh4ocpeI (visad 2023-06-30) Weber-Wulff, D., Anohina-Naumeca, A., Bjelobaba, S., Foltýnek, T., Guerrero-Dib, J., Popoola, O., Šigut, P., & Waddington, L. (2023). Testing of Detection Tools for AI�Generated Text (arXiv:2306.15666). arXiv. https://doi.org/10.48550/arXiv.2306.1566
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38. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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39. |
- Suhonen, Riitta, et al.
(författare)
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Cross-cultural validity of the Individualised Care Scale – a Rasch model analysis
- 2013
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Ingår i: Journal of Clinical Nursing. - : Wiley-Blackwell. - 0962-1067 .- 1365-2702. ; 22:5-6, s. 648-660
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Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives. The aim of this study was to investigate, using Rasch model analysis, the measurement invariance of the item ratings of the Individualised Care Scale. Background. Evidence of reliability is needed in cross-cultural comparative studies. To be used in different cultures and languages, the items must function the same way. Design. A methodological and comparative design. Methods. Secondary analysis of data, gathered in 2005–2006 from a cross-cultural survey using the Individualised Care Scale from Finnish, Greek, Swedish and English predischarge hospitalised orthopaedic and trauma patients (n = 1093), was used. The Rasch model, which produces calibrations (item locations and rank) and item fit statistics, was computed using the Winstep program. Results. The rank of average Individualised Care Scale item calibrations (−2·26–1·52) followed a generally similar trend (Infit ≤ 1·3), but slight differences in the item rank by country were found and some item misfit was identified within the same items. There was some variation in the order and location of some Individualised Care Scale items for individual countries, but the overall pattern of item calibration was generally corresponding. Conclusions. The Rasch model provided information about the appropriateness, sensitivity and item function in different cultures providing more in-depth information about the psychometric properties of the Individualised Care Scale instrument. Comparison of the four versions of the Individualised Care Scale – patient revealed general correspondence in the item calibration patterns although slight differences in the rank order of the items were found. Some items showed also a slight misfit. Based on these results, the phrasing and targeting of some items should be considered. Relevance to clinical practice. The Individualised Care Scale – Patient version can be used in cross-cultural studies for the measurement of patients’ perceptions of individualised care. Information obtained with the use of the Individualised Care Scale in clinical nursing practice is important, and valid measures are needed in evaluating patients’ assessment of individualised care, one indicator of care quality.
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40. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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