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  1. Article ; Online: Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake.

    Bojsen-Møller, Kirstine Nyvold / Svane, Maria Saur / Martinussen, Christoffer / Dirksen, Carsten / Jørgensen, Nils Bruun / Jensen, Jens-Erik Beck / Jensen, Christian Zinck / Torekov, Signe Sørensen / Kristiansen, Viggo Bjerregaard / Rehfeld, Jens Frederik / Bork-Jensen, Jette / Grarup, Niels / Hansen, Torben / Hartmann, Bolette / Holst, Jens Juul / Madsbad, Sten

    International journal of obesity (2005)

    2023  Volume 47, Issue 11, Page(s) 1143–1151

    Abstract: Background/objectives: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon- ... ...

    Abstract Background/objectives: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.
    Subjects/methods: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.
    Results: On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).
    Conclusions: Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.
    MeSH term(s) Humans ; Female ; Gastric Bypass ; Ghrelin ; Octreotide/pharmacology ; Gastrointestinal Hormones ; Peptide YY ; Glucagon-Like Peptide 1 ; Cholecystokinin ; Eating ; Weight Loss/physiology
    Chemical Substances Ghrelin ; Octreotide (RWM8CCW8GP) ; Gastrointestinal Hormones ; Peptide YY (106388-42-5) ; Glucagon-Like Peptide 1 (89750-14-1) ; Cholecystokinin (9011-97-6)
    Language English
    Publishing date 2023-08-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 752409-2
    ISSN 1476-5497 ; 0307-0565
    ISSN (online) 1476-5497
    ISSN 0307-0565
    DOI 10.1038/s41366-023-01372-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity.

    Andersen, Mette K / Ängquist, Lars / Bork-Jensen, Jette / Jonsson, Anna E / Stinson, Sara E / Sandholt, Camilla H / Thodberg, Malte / Pikkupeura, Laura Maarit / Ongstad, Emily L / Grarup, Niels / Astrup, Arne / Pedersen, Oluf / Williams, Kristine / Barrès, Romain / Sørensen, Thorkild I A / Linneberg, Allan / Grimsby, Joseph / Rhodes, Christopher J / Hansen, Torben

    Diabetes care

    2023  Volume 46, Issue 5, Page(s) 985–992

    Abstract: Objective: The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, to assess whether PA and/or IS modify the association ... ...

    Abstract Objective: The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, to assess whether PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms.
    Research design and methods: Genetic association analyses comprised up to 19,585 individuals. PA was self-reported, and IS was defined based on inverted HOMA insulin resistance index. Functional analyses were performed in muscle biopsies from 140 men and in cultured muscle cells.
    Results: The BMI-increasing effect of the FTO rs9939609 A allele was attenuated by 47% with high PA (β [SE], -0.32 [0.10] kg/m2, P = 0.0013) and by 51% with high IS (-0.31 [0.09] kg/m2, P = 0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 [0.09] kg/m2, P = 0.023; IS, -0.28 [0.09] kg/m2, P = 0.0011). The rs9939609 A allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, P > 0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A allele was associated with higher expression of FTO in skeletal muscle tissue (0.03 [0.01], P = 0.011), and in skeletal muscle cells, we identified a physical interaction between the FTO promoter and an enhancer region encompassing rs9939609.
    Conclusions: Greater PA and IS independently reduced the effect of rs9939609 on obesity. These effects might be mediated through altered expression of FTO in skeletal muscle. Our results indicated that PA and/or other means of increasing insulin sensitivity could counteract FTO-related genetic predisposition to obesity.
    MeSH term(s) Male ; Humans ; Insulin Resistance/genetics ; Body Mass Index ; Obesity/genetics ; Obesity/metabolism ; Exercise ; Genetic Predisposition to Disease ; Insulin/genetics ; Insulin, Regular, Human ; Hyperinsulinism ; Cardiovascular Diseases ; Polymorphism, Single Nucleotide ; Genotype ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
    Chemical Substances Insulin ; Insulin, Regular, Human ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO (EC 1.14.11.33) ; FTO protein, human (EC 1.14.11.33)
    Language English
    Publishing date 2023-02-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 441231-x
    ISSN 1935-5548 ; 0149-5992
    ISSN (online) 1935-5548
    ISSN 0149-5992
    DOI 10.2337/dc22-2078
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rare Heterozygous Loss-of-Function Variants in the Human GLP-1 Receptor Are Not Associated With Cardiometabolic Phenotypes.

    Melchiorsen, Josefine U / Sørensen, Kimmie V / Bork-Jensen, Jette / Kizilkaya, Hüsün S / Gasbjerg, Lærke S / Hauser, Alexander S / Rungby, Jørgen / Sørensen, Henrik T / Vaag, Allan / Nielsen, Jens S / Pedersen, Oluf / Linneberg, Allan / Hartmann, Bolette / Gjesing, Anette P / Holst, Jens J / Hansen, Torben / Rosenkilde, Mette M / Grarup, Niels

    The Journal of clinical endocrinology and metabolism

    2023  Volume 108, Issue 11, Page(s) 2821–2833

    Abstract: Context: Lost glucagon-like peptide 1 receptor (GLP-1R) function affects human physiology.: Objective: This work aimed to identify coding nonsynonymous GLP1R variants in Danish individuals to link their in vitro phenotypes and clinical phenotypic ... ...

    Abstract Context: Lost glucagon-like peptide 1 receptor (GLP-1R) function affects human physiology.
    Objective: This work aimed to identify coding nonsynonymous GLP1R variants in Danish individuals to link their in vitro phenotypes and clinical phenotypic associations.
    Methods: We sequenced GLP1R in 8642 Danish individuals with type 2 diabetes or normal glucose tolerance and examined the ability of nonsynonymous variants to bind GLP-1 and to signal in transfected cells via cyclic adenosine monophosphate (cAMP) formation and β-arrestin recruitment. We performed a cross-sectional study between the burden of loss-of-signaling (LoS) variants and cardiometabolic phenotypes in 2930 patients with type 2 diabetes and 5712 participants in a population-based cohort. Furthermore, we studied the association between cardiometabolic phenotypes and the burden of the LoS variants and 60 partly overlapping predicted loss-of-function (pLoF) GLP1R variants found in 330 566 unrelated White exome-sequenced participants in the UK Biobank cohort.
    Results: We identified 36 nonsynonymous variants in GLP1R, of which 10 had a statistically significant loss in GLP-1-induced cAMP signaling compared to wild-type. However, no association was observed between the LoS variants and type 2 diabetes, although LoS variant carriers had a minor increased fasting plasma glucose level. Moreover, pLoF variants from the UK Biobank also did not reveal substantial cardiometabolic associations, despite a small effect on glycated hemoglobin A1c.
    Conclusion: Since no homozygous LoS nor pLoF variants were identified and heterozygous carriers had similar cardiometabolic phenotype as noncarriers, we conclude that GLP-1R may be of particular importance in human physiology, due to a potential evolutionary intolerance of harmful homozygous GLP1R variants.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 2/genetics ; Glucagon-Like Peptide-1 Receptor/genetics ; Glucagon-Like Peptide-1 Receptor/metabolism ; Cross-Sectional Studies ; Glucagon-Like Peptide 1/metabolism ; Phenotype ; Cardiovascular Diseases
    Chemical Substances Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptide 1 (89750-14-1)
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/clinem/dgad290
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism.

    Williams, Kristine / Ingerslev, Lars R / Bork-Jensen, Jette / Wohlwend, Martin / Hansen, Ann Normann / Small, Lewin / Ribel-Madsen, Rasmus / Astrup, Arne / Pedersen, Oluf / Auwerx, Johan / Workman, Christopher T / Grarup, Niels / Hansen, Torben / Barrès, Romain

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 2695

    Abstract: Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated ... ...

    Abstract Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority are located in non-coding DNA regions. This suggests that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism.
    MeSH term(s) Animals ; Cell Line ; Chromatin/genetics ; Chromatin/metabolism ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Enhancer Elements, Genetic ; Female ; Gene Expression Profiling ; Genome-Wide Association Study ; Humans ; Insulin Resistance/genetics ; Male ; Mice ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/metabolism ; Obesity/genetics ; Obesity/metabolism ; Obesity/pathology ; Palmitic Acid/pharmacology ; Peptide Initiation Factors/genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha/pharmacology
    Chemical Substances Chromatin ; Itgb4bp protein, mouse ; Peptide Initiation Factors ; Tumor Necrosis Factor-alpha ; Palmitic Acid (2V16EO95H1)
    Language English
    Publishing date 2020-06-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-16537-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB.

    Eliasen, Anders U / Pedersen, Casper Emil T / Rasmussen, Morten A / Wang, Ni / Soverini, Matteo / Fritz, Amelie / Stokholm, Jakob / Chawes, Bo L / Morin, Andréanne / Bork-Jensen, Jette / Grarup, Niels / Pedersen, Oluf / Hansen, Torben / Linneberg, Allan / Mortensen, Preben B / Hougaard, David M / Bybjerg-Grauholm, Jonas / Bækvad-Hansen, Marie / Mors, Ole /
    Nordentoft, Merete / Børglum, Anders D / Werge, Thomas / Agerbo, Esben / Söderhall, Cilla / Altman, Matthew C / Thysen, Anna H / McKennan, Chris G / Brix, Susanne / Gern, James E / Ober, Carole / Ahluwalia, Tarunveer S / Bisgaard, Hans / Pedersen, Anders G / Bønnelykke, Klaus

    The Journal of allergy and clinical immunology

    2022  Volume 150, Issue 3, Page(s) 622–630

    Abstract: Background: Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in ...

    Abstract Background: Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measures are inadequate.
    Objective: We sought to identify genetic interaction associated with the development of childhood asthma.
    Methods: We performed an exhaustive search for pairwise interaction between genetic single nucleotide polymorphisms using 1204 cases of a specific phenotype of early childhood asthma with severe exacerbations in patients aged 2 to 6 years combined with 5328 nonasthmatic controls. Replication was attempted in 3 independent populations, and potential underlying immune mechanisms were investigated in the COPSAC2010 and COPSAC2000 birth cohorts.
    Results: We found evidence of interaction, including replication in independent populations, between the known childhood asthma loci CDHR3 and GSDMB. The effect of CDHR3 was dependent on the GSDMB genotype, and this interaction was more pronounced for severe and early onset of disease. Blood immune analyses suggested a mechanism related to increased IL-17A production after viral stimulation.
    Conclusions: We found evidence of interaction between CDHR3 and GSDMB in development of early childhood asthma, possibly related to increased IL-17A response to viral infections. This study demonstrates the importance of focusing on specific disease subtypes for understanding the genetic mechanisms of asthma.
    MeSH term(s) Asthma/genetics ; Cadherin Related Proteins ; Cadherins/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Interleukin-17/genetics ; Membrane Proteins/genetics ; Neoplasm Proteins/genetics ; Polymorphism, Single Nucleotide ; Pore Forming Cytotoxic Proteins
    Chemical Substances CDHR3 protein, human ; Cadherin Related Proteins ; Cadherins ; GSDMB protein, human ; Interleukin-17 ; Membrane Proteins ; Neoplasm Proteins ; Pore Forming Cytotoxic Proteins
    Language English
    Publishing date 2022-04-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2022.03.019
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  6. Article ; Online: Carriers of a

    Ahluwalia, Tarunveer Singh / Troelsen, Jesper Thorvald / Balslev-Harder, Marie / Bork-Jensen, Jette / Thuesen, Betina Heinsbæk / Cerqueira, Charlotte / Linneberg, Allan / Grarup, Niels / Pedersen, Oluf / Hansen, Torben / Dalgaard, Louise Torp

    Journal of medical genetics

    2017  Volume 54, Issue 3, Page(s) 166–175

    Abstract: Background: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (: Methods: We performed an association ... ...

    Abstract Background: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (
    Methods: We performed an association study of the
    Results: Four SNPs in
    Conclusions: VEGF is an important angiogenic signal required for tissue expansion. We show that
    Trial registration number: NCT00289237, NCT00316667; Results.
    Language English
    Publishing date 2017-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 220881-7
    ISSN 1468-6244 ; 0022-2593
    ISSN (online) 1468-6244
    ISSN 0022-2593
    DOI 10.1136/jmedgenet-2016-104084
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  7. Article: The morphogenetic MreBCD proteins of Escherichia coli form an essential membrane-bound complex.

    Kruse, Thomas / Bork-Jensen, Jette / Gerdes, Kenn

    Molecular microbiology

    2005  Volume 55, Issue 1, Page(s) 78–89

    Abstract: MreB proteins of Escherichia coli, Bacillus subtilis and Caulobacter crescentus form actin-like cables lying beneath the cell surface. The cables are required to guide longitudinal cell wall synthesis and their absence leads to merodiploid spherical and ... ...

    Abstract MreB proteins of Escherichia coli, Bacillus subtilis and Caulobacter crescentus form actin-like cables lying beneath the cell surface. The cables are required to guide longitudinal cell wall synthesis and their absence leads to merodiploid spherical and inflated cells prone to cell lysis. In B. subtilis and C. crescentus, the mreB gene is essential. However, in E. coli, mreB was inferred not to be essential. Using a tight, conditional gene depletion system, we systematically investigated whether the E. coli mreBCD-encoded components were essential. We found that cells depleted of mreBCD became spherical, enlarged and finally lysed. Depletion of each mre gene separately conferred similar gross changes in cell morphology and viability. Thus, the three proteins encoded by mreBCD are all essential and function in the same morphogenetic pathway. Interestingly, the presence of a multicopy plasmid carrying the ftsQAZ genes suppressed the lethality of deletions in the mre operon. Using GFP and cell fractionation methods, we showed that the MreC and MreD proteins were associated with the cell membrane. Using a bacterial two-hybrid system, we found that MreC interacted with both MreB and MreD. In contrast, MreB and MreD did not interact in this assay. Thus, we conclude that the E. coli MreBCD form an essential membrane-bound complex. Curiously, MreB did not form cables in cell depleted for MreC, MreD or RodA, indicating a mutual interdependency between MreB filament morphology and cell shape. Based on these and other observations we propose a model in which the membrane-associated MreBCD complex directs longitudinal cell wall synthesis in a process essential to maintain cell morphology.
    MeSH term(s) Amino Acid Sequence ; Cell Membrane/metabolism ; Escherichia coli/cytology ; Escherichia coli/genetics ; Escherichia coli/physiology ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/physiology ; Genes, Bacterial ; Green Fluorescent Proteins/genetics ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Suppression, Genetic ; Two-Hybrid System Techniques
    Chemical Substances Escherichia coli Proteins ; FtsA protein, E coli ; FtsQ protein, E coli ; FtsZ84 protein, E coli ; Membrane Proteins ; MreD protein, E coli ; Green Fluorescent Proteins (147336-22-9) ; MreB protein, E coli (149255-61-8)
    Language English
    Publishing date 2005-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/j.1365-2958.2004.04367.x
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  8. Article ; Online: Linking glycemic dysregulation in diabetes to symptoms, comorbidities, and genetics through EHR data mining.

    Kirk, Isa Kristina / Simon, Christian / Banasik, Karina / Holm, Peter Christoffer / Haue, Amalie Dahl / Jensen, Peter Bjødstrup / Juhl Jensen, Lars / Rodríguez, Cristina Leal / Pedersen, Mette Krogh / Eriksson, Robert / Andersen, Henrik Ullits / Almdal, Thomas / Bork-Jensen, Jette / Grarup, Niels / Borch-Johnsen, Knut / Pedersen, Oluf / Pociot, Flemming / Hansen, Torben / Bergholdt, Regine /
    Rossing, Peter / Brunak, Søren

    eLife

    2019  Volume 8

    Abstract: Diabetes is a diverse and complex disease, with considerable variation in phenotypic manifestation and severity. This variation hampers the study of etiological differences and reduces the statistical power of analyses of associations to genetics, ... ...

    Abstract Diabetes is a diverse and complex disease, with considerable variation in phenotypic manifestation and severity. This variation hampers the study of etiological differences and reduces the statistical power of analyses of associations to genetics, treatment outcomes, and complications. We address these issues through deep, fine-grained phenotypic stratification of a diabetes cohort. Text mining the electronic health records of 14,017 patients, we matched two controlled vocabularies (ICD-10 and a custom vocabulary developed at the clinical center Steno Diabetes Center Copenhagen) to clinical narratives spanning a 19 year period. The two matched vocabularies comprise over 20,000 medical terms describing symptoms, other diagnoses, and lifestyle factors. The cohort is genetically homogeneous (Caucasian diabetes patients from Denmark) so the resulting stratification is not driven by ethnic differences, but rather by inherently dissimilar progression patterns and lifestyle related risk factors. Using unsupervised Markov clustering, we defined 71 clusters of at least 50 individuals within the diabetes spectrum. The clusters display both distinct and shared longitudinal glycemic dysregulation patterns, temporal co-occurrences of comorbidities, and associations to single nucleotide polymorphisms in or near genes relevant for diabetes comorbidities.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Child ; Cohort Studies ; Data Mining ; Denmark/epidemiology ; Diabetes Complications/diagnosis ; Diabetes Complications/epidemiology ; Diabetes Complications/genetics ; Diabetes Complications/therapy ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus/genetics ; Diabetes Mellitus/therapy ; Electronic Health Records ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Terminology as Topic ; Treatment Outcome ; Vocabulary ; Young Adult
    Language English
    Publishing date 2019-12-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.44941
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  9. Article ; Online: FUT2-ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses.

    Ahluwalia, Tarunveer S / Eliasen, Anders U / Sevelsted, Astrid / Pedersen, Casper-Emil T / Stokholm, Jakob / Chawes, Bo / Bork-Jensen, Jette / Grarup, Niels / Pedersen, Oluf / Hansen, Torben / Linneberg, Allan / Sharma, Amitabh / Weiss, Scott T / Evans, Michael D / Jackson, Daniel J / Morin, Andreanne / Krogfelt, Karen A / Schjørring, Susanne / Mortensen, Preben B /
    Hougaard, David M / Bybjerg-Grauholm, Jonas / Bækvad-Hansen, Marie / Mors, Ole / Nordentoft, Merete / Børglum, Anders D / Werge, Thomas / Agerbo, Esben / Gern, James E / Lemanske, Robert F / Ober, Carole / Pedersen, Anders G / Bisgaard, Hans / Bønnelykke, Klaus

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 6398

    Abstract: Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises ... ...

    Abstract Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11-1.25), P
    MeSH term(s) ABO Blood-Group System/genetics ; Asthma/genetics ; Case-Control Studies ; Child ; Child, Preschool ; Epistasis, Genetic ; Female ; Fucosyltransferases/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Pneumococcal Infections/genetics ; Polymorphism, Single Nucleotide ; Streptococcus pneumoniae/pathogenicity ; Galactoside 2-alpha-L-fucosyltransferase
    Chemical Substances ABO Blood-Group System ; Fucosyltransferases (EC 2.4.1.-)
    Language English
    Publishing date 2020-12-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-19814-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study.

    Bork-Jensen, Jette / Thuesen, Anne Cathrine Baun / Bang-Bertelsen, Claus Heiner / Grunnet, Louise Groth / Pociot, Flemming / Beck-Nielsen, Henning / Ozanne, Susan E / Poulsen, Pernille / Vaag, Allan

    Genes

    2014  Volume 5, Issue 3, Page(s) 508–517

    Abstract: Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ...

    Abstract Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resistance and T2D. We aimed to explore the genetic and non-genetic factors that regulate these microRNAs in human SAT, and to investigate their impact on metabolism in humans. Levels of miR-103, miR-143 and miR-483-3p were measured in SAT biopsies from 244 elderly monozygotic and dizygotic twins using real-time PCR. Heritability estimates were calculated and multiple regression analyses were performed to study associations between these microRNAs and measures of metabolism, as well as between these microRNAs and possible regulating factors. We found that increased BMI was associated with increased miR-103 expression levels. In addition, the miR-103 levels were positively associated with 2 h plasma glucose levels and hemoglobin A1c independently of BMI. Heritability estimates for all three microRNAs were low. In conclusion, the expression levels of miR-103, miR-143 and miR-483-3p in adipose tissue are primarily influenced by non-genetic factors, and miR-103 may be involved in the development of adiposity and control of glucose metabolism in humans.
    Language English
    Publishing date 2014-07-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes5030508
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