| 1. |
- Wain, Louise V, et al.
(författare)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 2. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 3. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 4. |
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| 5. |
- Gunnbjörnsdottir, Maria I, et al.
(författare)
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Indoor environment in three North European cities in relationship to atopy and respiratory symptoms
- 2009
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Ingår i: Clinical Respiratory Journal. - 1752-6981. ; 3:2, s. 85-94
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Tidskriftsartikel (refereegranskat)abstract
- In the European Community Respiratory Health Survey (ECRHS) I, the lowest prevalence of asthma and atopy was found in Reykjavik (Iceland) and Tartu (Estonia). The aim of this study was to compare home environments in Reykjavik and Tartu to a town with a higher prevalence of asthma and atopy (Uppsala, Sweden) in an attempt to identify factors in the indoor environment that could explain these differences. A random sample of 129 ECRHS II participants was included in this analysis at each of the three study centres. The subjects answered a questionnaire, blood was analysed for specific immunoglobulin E, a methacholine test was performed and home indoor measurements were taken. The prevalence of atopy was 11.9% in Reykjavik, 35.5% in Uppsala and 28.2% in Tartu (P < 0.04). The level of indoor cat allergen was significantly lower in Reykjavik compared with Uppsala (P = 0.05). No mite allergens were identified in the 41 homes investigated in Reykjavik, while this was the case in 16% and 72% of the households in Uppsala and Tartu, respectively (P = 0.001). A positive association was found between asthma symptoms and cat allergen levels [odds ratio 1.53 (95% confidence interval 1.04-2.24)], while the levels of viable moulds were significantly associated with increased bronchial responsiveness. Indoor exposure to allergens, moulds and bacteria was lower in Reykjavik than in the Swedish and Estonian centres. This finding indicates that the lower prevalence of allergic sensitization in Reykjavik may partly be related to lower indoor allergen exposure. Please cite this paper as: Gunnbjornsdottir MI, NorbAck D, Bjornsson E, Soon A, Jarvis D, Jogi R, Gislason D, Gislason T and Janson C. Indoor environment in three North European cities in relationship to atopy and respiratory symptoms. The Clinical Respiratory Journal 2009; 3: 85-94.
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| 6. |
- Jogi, Nils Oskar, et al.
(författare)
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Prevalence of allergic sensitization to storage mites in Northern Europe
- 2020
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 50:3, s. 372-382
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAllergic sensitization to storage mites has mostly been related to occupational exposures like farming, grain/cattle handling, whereas for non‐occupational settings, storage mite sensitization has been attributed to cross‐reactivity with house dust mite (HDM) allergens.ObjectiveWe aimed to describe the prevalence of allergic sensitization to storage mites, co‐sensitization to HDM allergens and respiratory symptoms in Denmark, Iceland, Norway and Sweden.MethodsThe population comprised of 1180 participants born 1945‐1972 of the third follow‐up of the population‐based cohort European Community Respiratory Health Survey (ECRHS) in Aarhus, Bergen, Reykjavik and Uppsala. A clinical examination included skin prick tests (SPT) to Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro and common inhalant allergens, as well as standardized interviews.Results8% were sensitized to HDM and 10% to storage mite, with some variation by study centre: Reykjavik 13%, Bergen 8% and Aarhus 7%. In Uppsala, only L destructor (3%) was measured. Storage mite sensitization was higher among men (11%) than women (8%). Among storage mite sensitized, 44% were also sensitized to HDM. Storage mite sensitization was associated with asthma and nasal allergies, but not with age, education, pet keeping or place of upbringing.Conclusions and Clinical RelevanceIn this Northern European population‐based study, allergic sensitization to storage mite was as common as HDM sensitization. Storage mite sensitization was, independently of HDM sensitization, associated with respiratory symptoms and asthma. Our findings suggest that storage mite sensitization should be evaluated with regard to inclusion into the common inhalant allergen panel in Northern Europe.
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| 7. |
- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 8. |
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| 9. |
- Olafsdottir, Inga Sif, et al.
(författare)
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Gender differences in the association between C-reactive protein, lung function impairment, and COPD
- 2007
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106. ; 2:4, s. 635-642
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with COPD have systemic inflammation that can be assessed by measuring C-reactive protein (CRP). In this paper we evaluated whether CRP is related to COPD, lung function and rate of lung function decline. We included 1237 randomly selected subjects (mean age 42, range 28–56 years) from three centers in the European Community Respiratory Health Survey: Reykjavik, Uppsala and Tartu. CRP was measured at the end of the follow-up (mean 8.3 years) and the values were divided into 4 quartiles. Fifty-three non-asthmatic subjects fulfilled spirometric criteria for COPD (FEV1/FVC < 70%). COPD occurred more often in the 4th CRP quartile (OR (95% CI) 3.21 (1.13–9.08)) after adjustment for age, gender, body weight and smoking. High CRP levels were related to lower FEV1 values in both men (−437 (−596, −279) mL) and women (−144 (−243, −44) mL). The negative association between CRP and FEV1 was significantly larger in men than women (p = 0.04). The decline in FEV1 was larger (16 (5, 27) mL) in men with high CRP levels whereas no significant association between CRP and FEV1 decline was found in women. Higher CRP values are significantly associated with COPD and lower lung function in men and women. In men higher CRP values are related to a larger decline in FEV1.
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| 10. |
- Thjodleifsson, Bjarni, et al.
(författare)
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Infections and obesity : A multinational epidemiological study
- 2008
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 40:5, s. 381-386
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Viral infections have been associated with the aetiology of obesity in animal models. This study investigates the association between 7 serological markers of infections and body mass index (BMI) in a population based sample. Individuals (n=985, mean age 42+/-97 (28-55) y, mean BMI 25.594.2) from Iceland, Sweden and Estonia underwent a structured interview and blood sampling. IgG antibodies were measured against Helicobacter pylori and the cagA protein, hepatitis A virus, Toxoplasma gondii, herpes simplex virus 1, Chlamydia pneumoniae, Epstein-Barr virus and cytomegalovirus. High-sensitive C-reactive protein (CRP) was measured as a marker of systemic inflammation. A significant positive association between being overweight (BMI25 kg/m2) and IgG antibodies was found for Helicobacter pylori (OR 1.86, CI 1.34-2.60) and Chlamydia pneumoniae (OR 1.39, CI 1.03-1.88) and combined seropositivity had synergistic effect (OR 2.54 (1.62-3.97)). CRP was positively related to BMI (pB0.0001), whereas no significant association was found between CRP and IgG antibodies against Helicobacter pylori and/or Chlamydia pneumoniae and CRP. The results suggest that infections with Chlamydia pneumoniae and Helicobacter pylori are both significantly and synergistically associated with overweight and this association is not related to indicators of systemic inflammation.
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