| 1. |
- Clason, Caroline C., et al.
(författare)
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Dye tracing to determine flow properties of hydrocarbon-polluted Rabots glaciar, Kebnekaise, Sweden
- 2015
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Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 19:6, s. 2701-2715
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Tidskriftsartikel (refereegranskat)abstract
- Over 11 000 L of kerosene was deposited on the surface of Rabots glaciar on the Kebnekaise Massif, northern Sweden, following the crash of a Royal Norwegian Air Force aircraft in March 2012. An environmental monitoring programme was subsequently commissioned, including a series of dye tracing experiments during the 2013 melt season, conducted to investigate the transport of pollutants through the glacier hydrological system. This experimental set-up provided a basis from which we could gain new insight into the internal hydrological system of Rabots glaciar. Results of dye tracing experiments reveal a degree of homogeneity in the topology of the drainage system throughout July and August, with an increase in efficiency as the season progresses, as reflected by decreasing temporary storage and dispersivity. Early onset of melting likely led to formation of an efficient, discrete drainage system early in the melt season, subject to decreasing sinuosity and braiding as the season progressed. Four distinct meltwater flow regimes are identified to summarize the temporal and spatial evolution of the system. Analysis of turbidity-discharge hysteresis further supports the formation of discrete, efficient drainage, with clockwise diurnal hysteresis suggesting easy mobilization of readily available sediments in channels. Dye injection immediately downstream of the pollution source zone reveals prolonged storage of dye followed by fast, efficient release. Twinned with a low dye recovery, and supported by sporadic detection of hydrocarbons in the proglacial river, we suggest that meltwater, and thus pollutants in solution, may be released periodically through an efficient, and likely pressurized, hydrological system within the upper reaches of the glacier.
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| 2. |
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| 3. |
- Backman, Helena, et al.
(författare)
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A population-based cohort of adults with asthma: mortality and participation in a long-term follow-up
- 2017
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Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Asthma is a major public health concern. The aim of this study was to characterize a large population-based cohort of adults with asthma, and to study factors associated with all-cause mortality and non-participation in a long-term follow-up. Design: Random and stratified samples from five population-based cohorts were clinically examined during 1986-2001, and all subjects with asthma were included in the study (n = 2055, age 19-72 years, 55% women). Independent associations between different risk factors and (i) mortality and (ii) non-participation in a clinical follow-up in 2012-2014 were estimated. Results: In 1986-2001, 95% reported any wheeze and/or attacks of shortness of breath in the past 12 months, and/or asthma medication use. Over the up to 28 years of follow-up time, the cumulative mortality was 22.7%. Male gender, current smoking, and lower forced expiratory volume in 1 sec of predicted (FEV1% of predicted) were independent risk factors for mortality, while obesity was associated with non-participation in the follow-up. Older ages, ischemic heart disease, and low socioeconomic status were associated with both mortality and non-participation. Conclusions: The risk factors associated with mortality in this adult population-based asthma cohort were similar to those commonly identified in general population samples, i.e. male gender, current smoking, and lower FEV1% of predicted, while obesity was associated with non-participation in a long-term follow-up. Ischemic heart disease, low socioeconomic status, and older ages were associated with both mortality and non-participation.
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| 4. |
- Backman, Helena, et al.
(författare)
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Chronic airway obstruction in a population-based adult asthma cohort : Prevalence, incidence and prognostic factors
- 2018
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Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 138, s. 115-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAsthma and COPD may overlap (ACO) but information about incidence and risk factors are lacking. This study aimed to estimate prevalence, incidence and risk factors of chronic airway obstruction (CAO) in a population-based adult asthma cohort.MethodsDuring 1986–2001 a large population-based asthma cohort was identified (n = 2055, 19-72y). Subsamples have participated in clinical follow-ups during the subsequent years. The entire cohort was invited to a clinical follow-up including interview, spirometry, and blood sampling in 2012–2014 when n = 983 subjects performed adequate spirometry. CAO was defined as post-bronchodilator FEV1/FVC<0.7.ResultsAt study entry, asthmatics with prevalent CAO (11.4%) reported more respiratory symptoms, asthma medication use, and ischemic heart disease than asthmatics without CAO (asthma only). Subjects who developed CAO during follow-up (17.6%; incidence rate of 16/1000/year) had a more rapid FEV1 decline and higher levels of neutrophils than asthma only. Smoking, older age and male sex were independently associated with increased risk for both prevalent and incident CAO, while obesity had a protective effect.ConclusionsIn this prospective adult asthma cohort, the majority did not develop CAO. Smoking, older age and male sex were risk factors for prevalent and incident CAO, similar to risk factors described for COPD in the general population.
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| 5. |
- Backman, Helena, et al.
(författare)
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Decreased prevalence of moderate to severe COPD over 15 years in northern Sweden
- 2016
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 114, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: The burden of COPD in terms of mortality, morbidity, costs and prevalence has increased worldwide. Recent results on prevalence in Western Europe are conflicting. In Sweden smoking prevalence has steadily decreased over the past 30 years. Aim: The aim was to study changes in prevalence and risk factor patterns of COPD in the same area and within the same age-span 15 years apart. Material and methods: Two population-based cross-sectional samples in ages 23-72 years participating at examinations in 1994 and 2009, respectively, were compared in terms of COPD prevalence, severity and risk factor patterns. Two different definitions of COPD were used; FEV1/FVC < LLN and FEV1/FVC < 0.7. The severity of COPD was assessed by FEV1, both as % of predicted and in relation to the LLN. Results: The prevalence of COPD decreased significantly from 9.5% to 6.3% (p = 0.030) according to the FEV1/FVC < LLN criterion, while the decrease based on the FEV1/FVC < 0.7 criterion from 10.5% to 8.5% was non-significant. The prevalence of moderate to severe COPD decreased substantially and significantly, and the risk factor pattern was altered in 2009 when, beside age and smoking, also socioeconomic status based on occupation was significantly associated with COPD. Conclusions: Changes in both prevalence and risk factor patterns of COPD were observed between surveys. Following a continuing decrease in smoking habits over several decades, a decrease in the prevalence of moderate to severe COPD was observed from 1994 to 2009 in northern Sweden.
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| 6. |
- Backman, Helena, et al.
(författare)
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Eosinophilic inflammation and lung function decline in a long-term follow-up of a large population-based asthma cohort
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The relationship between lung function decline and airway inflammation among asthmatics has important therapeutic implications, but has rarely been studied in large samples or in population-based asthma cohorts.A population-based adult asthma cohort (n=2055) was recruited during 1986-2001 and clinically examined including spirometry. In 2012-2014, all still eligible subjects (n=1425) were invited to a clinical follow-up including spirometry, blood sampling, and a structured interview, and n=1006 participated (55% women, mean age 59y, 32-92y). Linear regression was performed with age, sex, smoking habits, year of first examination, family history of asthma, socioeconomic status, eosinophils (EOS)>=0.3x109/L, and neutrophils (NEUT)>=5.0x109/L as independent variables and pre-bronchodilator FEV1 decline/year (ml and % of predicted [pp], respectively) as dependent. In secondary models, both ICS use at baseline and ICS use at follow-up were also included.The mean annual FEV1 decline in ml (pp) among asthmatics with EOS<0.3, 0.4>EOS>=0.3 and EOS>=0.4x109/L, respectively, was 26ml (0.03pp), 29ml (0.10pp) and 34ml (0.27pp) (p<0.001). In adjusted analyses, EOS>=0.3 was significantly associated with FEV1 decline, both in terms of ml (4ml excess annual decline vs EOS<0.3) and pp. The association between EOS and FEV1 decline in pp, but not ml, remained when additionally adjusted for ICS use. The association with NEUT>=5.0x109/L was less clear.On group level, adult asthmatics with higher levels of eosinophils in blood have a history of excess FEV1 decline compared to asthmatics with lower levels of eosinophil inflammation, independent of other factors such as ICS use.
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| 7. |
- Backman, Helena, et al.
(författare)
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Restrictive spirometric pattern in the general adult population: Methods of defining the condition and consequences on prevalence
- 2016
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 120, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- Background Attempts have been made to use dynamic spirometry to define restrictive lung function, but the definition of a restrictive spirometric pattern (RSP) varies between studies such as BOLD and NHANES. The aim of this study was to estimate the prevalence and risk factors of RSP among adults in northern Sweden based on different definitions. Methods In 2008–2009 a general population sample aged 21–86y within the obstructive lung disease in northern Sweden (OLIN) studies was examined by structured interview and spirometry, and 726 subjects participated (71% of invited). The prevalence of RSP was calculated according to three different definitions based on pre-as well as post-bronchodilator spirometry: 1) FVC<80% & FEV1/FVC>0.7 2) FVC<80% & FEV1/FVC>LLN 3) FVCLLN Results The three definitions yielded RSP prevalence estimates of 10.5%, 11.2% and 9.4% respectively, when based on pre-bronchodilator values. The prevalence was lower when based on post-bronchodilator values, i.e. 7.3%, 7.9% and 6.6%. According to definition 1 and 2, the RSP prevalence increased by age, but not according to definition 3. The overlap between the definitions was substantial. When corrected for confounding factors, manual work in industry and diabetes with obesity were independently associated with an increased risk for RSP regardless of definition. Conclusions The prevalence of RSP was 7–11%. The prevalence estimates differed more depending on the choice of pre- compared to post-bronchodilator values than on the choice of RSP definition. RSP was, regardless of definition, independently associated with manual work in industry and diabetes with obesity. © 2016 The Authors
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| 8. |
- Backman, Helena, et al.
(författare)
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Severe asthma : A population study perspective
- 2019
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 49:6, s. 819-828
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSevere asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.ObjectiveTo describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.MethodsN=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.ResultsThe prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.Conclusions and clinical relevanceSevere asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.
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| 9. |
- Backman, Helena, et al.
(författare)
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Severe asthma among adults : Prevalence and clinical characteristics
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.Methods: We estimated the prevalence and studied characteristics of severe asthma in a large adult population-based asthma cohort followed for 10-28 years in northern Sweden: 1006 subjects participated in a follow-up during 2012-14, when 830 (82.5%) still had current asthma (mean age 59y, 32-92y, 56% women). Severe asthma was defined according to three internationally well-known criteria: the US SARP, ATS/ERS and GINA. All subjects with severe asthma were undergoing respiratory specialist care, and were also contacted by telephone to verify adherence to treatment.Results: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma and <10% had controlled asthma according to the ACT. Severe asthma was related to age >50 years, nasal polyposis, decreased FEV1, not fully reversible airway obstruction, sensitization to aspergillus, elevated neutrophils and partly to eosinophils, and tended to be more common in women.Conclusion: The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the population in northern Sweden. A substantial proportion of those with severe asthma had uncontrolled disease, and severe asthma differed significantly from other asthma in terms of both clinical and inflammatory characteristics.
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| 10. |
- Batool, Tahira, et al.
(författare)
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Upregulated BMP-Smad signaling activity in the glucuronyl C5-epimerase knock out MEF cells
- 2019
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Ingår i: Cellular Signalling. - : Elsevier. - 0898-6568 .- 1873-3913. ; 54, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce,in mice resulted in neonatal lethality with varied defects in organ development. To understand the molecular mechanisms of the phenotypes, we used mouse embryonic fibroblasts (MEF) as a model to examine selected signaling pathways. Our earlier studies found reduced activities of FGF-2, GDNF, but increased activity of sonic hedgehog in the mutant cells. In this study, we focused on the bone morphogenetic protein (BMP) signaling pathway. Western blotting detected substantially elevated endogenous Smad1/5/8 phosphorylation in the Hsepi mutant (KO) MEF cells, which is reverted by re-expression of the enzyme in the KO cells. The mutant cells displayed an enhanced proliferation and elevated alkaline phosphatase activity, marking higher differentiation, when cultured in osteogenic medium. The high level of Smad1/5/8 phosphorylation was also found in primary calvarial cells isolated from the KO mice. Analysis of the genes involved in the BMP signaling pathway revealed upregulation of a number of BMP ligands, but reduced expression of several Smads and BMP antagonist (Grem1) in the KO MEF cells. The results suggest that Hsepi expression modulates BMP signaling activity, which, at least partially, is associated with defected molecular structure of heparan sulfate expressed in the cells.
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| 11. |
- Bergenfelz, Caroline, et al.
(författare)
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Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.
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| 12. |
- Hamacher-Barth, Evelyne, et al.
(författare)
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Size-resolved morphological properties of the high Arctic summer aerosol during ASCOS-2008
- 2016
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:10, s. 6577-6593
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Tidskriftsartikel (refereegranskat)abstract
- The representation of aerosol properties and processes in climate models is fraught with large uncertainties. Especially at high northern latitudes a strong underprediction of aerosol concentrations and nucleation events is observed and can only be constrained by in situ observations based on the analysis of individual aerosol particles. To further reduce the uncertainties surrounding aerosol properties and their potential role as cloud condensation nuclei this study provides observational data resolved over size on morphological and chemical properties of aerosol particles collected in the summer high Arctic, north of 80A degrees aEuro-N. Aerosol particles were imaged with scanning and transmission electron microscopy and further evaluated with digital image analysis. In total, 3909 aerosol particles were imaged and categorized according to morphological similarities into three gross morphological groups: single particles, gel particles, and halo particles. Single particles were observed between 15 and 800aEuro-nm in diameter and represent the dominating type of particles (82aEuro-%). The majority of particles appeared to be marine gels with a broad Aitken mode peaking at 70aEuro-nm and accompanied by a minor fraction of ammonium (bi)sulfate with a maximum at 170aEuro-nm in number concentration. Gel particles (11aEuro-% of all particles) were observed between 45 and 800aEuro-nm with a maximum at 154aEuro-nm in diameter. Imaging with transmission electron microscopy allowed further morphological discrimination of gel particles in 'aggregate' particles, 'aggregate with film' particles, and 'mucus-like' particles. Halo particles were observed above 75aEuro-nm and appeared to be ammonium (bi)sulfate (59aEuro-% of halo particles), gel matter (19aEuro-%), or decomposed gel matter (22aEuro-%), which were internally mixed with sulfuric acid, methane sulfonic acid, or ammonium (bi)sulfate with a maximum at 161aEuro-nm in diameter. Elemental dispersive X-ray spectroscopy analysis of individual particles revealed a prevalence of the monovalent ions Na+/K+ for single particles and aggregate particles and of the divalent ions Ca2+/Mg2+ for aggregate with film particles and mucus-like particles. According to these results and other model studies, we propose a relationship between the availability of Na+/K+ and Ca2+/Mg2+ and the length of the biopolymer molecules participating in the formation of the three-dimensional gel networks.
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| 13. |
- Hedman, Linnea, 1979-, et al.
(författare)
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Population-based study shows that teenage girls with asthma had impaired health-related quality of life
- 2017
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:7, s. 1128-1135
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Tidskriftsartikel (refereegranskat)abstract
- AimThis study examined the health-related quality of life (HRQoL) of teenagers with and without asthma, including the impact of their sex, allergic conditions, smoking, living conditions and physical activity.MethodsThe Obstructive Lung Disease in Northern Sweden (OLIN) studies recruited a cohort of schoolchildren in 2006. The parents of all children aged seven to eight years in three municipalities were invited to complete a questionnaire and 2585 (96%) participated. The cohort was followed up at the ages of 11–12 years and 14–15 years with high participation rates. At 14–15 years, the HRQoL questionnaire KIDSCREEN-10 and Asthma Control Test were added.ResultsGirls with current asthma at 14–15 years had a lower mean HRQoL score than girls without asthma (46.4 versus 49.3, p < 0.001), but this was not seen among boys (53.8 versus 52.8, p = 0.373). Poor HRQoL was related to current asthma, uncontrolled asthma and teenage onset of asthma. It was also related to eczema, living in a single-parent household, maternal smoking, daily smoking and inversely related to physical activity.ConclusionTeenage girls with asthma had lower HRQoL than girls without asthma. Possible interventions to improve HRQoL among teenagers with asthma were identified as follows: increasing asthma control, preventing smoking and promoting physical activity.
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| 14. |
- Holmquist Mengelbier, Linda, et al.
(författare)
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Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.
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| 15. |
- Holmquist Mengelbier, Linda, et al.
(författare)
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The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis
- 2019
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 247:1
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Tidskriftsartikel (refereegranskat)abstract
- Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock-out Irx3−/Irx5− mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3−/− cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β-catenin-signalling. In contrast, IRX5−/− cells displayed activation of Hippo and non-canonical WNT-signalling and generated small tumours with abundant tubulogenesis. Our findings suggest that promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation.
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| 16. |
- Jakobsdottir, Johanna, et al.
(författare)
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Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
- 2016
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
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| 17. |
- Jansson, Caroline, 1963-
(författare)
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Experiences of Miscarriage
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Experiences are unique and both men and women experience grief, anxiety, depressive symptoms after a miscarriage.The overall aim was to describe and measure experiences among women and men after a miscarriage.Study one was a qualitative study with interviews with Swedish midwives' and nurses' experiences of women's reactions after routine ultrasonographic diagnosis of a missed miscarriage.Study two concerned validation of "The revised impact of miscarriage scale" for Swedish conditions and a comparison of Swedish and American women's and men's experiences of miscarriage.Study three was a longitudinal study of Swedish women's and men's emotions.Study four was a longitudinal study, on women's feelings in relation to diagnosis and treatment.Scales about experiences, grief, and depressive symptom were used.The results showed that midwives perceived that the women had had a premonition of symptoms of a missed miscarriage and a follow-up was performed. The degree of consistency showed that the questionnaire can be used in a Swedish setting. The Swedish and American women and men scored similarly in two factors, and the women's experiences were more pronounced than the men's. Grief and depressive symptoms became reduced over time, while experiences persisted. No previous children, miscarriage or infertility treatment prior to miscarriage made the experience worse especially grief reaction. There was no difference between the two diagnosis groups in experiences one week after the miscarriage and their experience improved after four months. Women treated with misoprostol had more depressive symptoms than women treated with misoprostol and subsequent vacuum aspiration.In conclusion, care providers can confirm women's premonition of a missed miscarriage so a diagnosis can be set early in the pregnancy and they can do an individual follow-up. The high consistency between the countries in two factors show that RIMS is reliable for both women and men. Grief and depressive symptoms become reduced, while experiences persist. Previous miscarriage, lack of previous children and an infertility diagnosis can lead to negative feelings as grief. A diagnosis of miscarriage has a limited influence on experiences, and a shorter duration of treatment and treatment with misoprostol and subsequent vacuum aspiration led to a fewer depressive symptom.
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| 18. |
- Jansson, Caroline, et al.
(författare)
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Validation of the Revised Impact of Miscarriage Scale for Swedish conditions and comparison between Swedish and American couples' experiences after miscarriage
- 2017
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Ingår i: European journal of contraception & reproductive health care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 22:6, s. 412-417
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is a lack of knowledge in women's and men's experience of miscarriage. The Revised Impact of Miscarriage Scale (RIMS) has been used in United States to measure the experiences after miscarriage. The first objective was to test the consistency of RIMS for Swedish conditions. The second purpose of this study was to compare Swedish and American couples' experience of miscarriage by use of the RIMS.METHODS: Forward and back translation was used for translating RIMS into Swedish. This is a hospital-based comparative study including Swedish couples (n = 70) and American couples (n = 70). The couples were matched by the women's age, week of miscarriage and number of children. All participants answered socio-demographic, fertility and depression-scale questions in addition to RIMS.RESULTS: Cronbach's alpha analysis was above 0.650, the mean value was 0.824. There was no significant difference between the Swedish and American participants on the factors 'Isolation/Guilt' and 'Devastating event', but the Swedish women and men scored significantly lower on the factor 'Loss of baby' than the American women and men. The men, Swedish and American combined, scored lower than the women in all factors but the correlation within the couples was similar for both Swedish and American couples.CONCLUSIONS: The high consistency between the countries suggests that the RIMS questionnaire is reliable for both women and men to be used in both countries and two of three factors were similar between the two countries.
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| 19. |
- Jansson, Desiree S., et al.
(författare)
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Post mortem findings and their relation to AA amyloidosis in free-ranging Herring gulls (Larus argentatus)
- 2018
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Since the late 1990s, high mortality and declining populations have been reported among sea birds including Herring gulls ( Larus argentatus) from the Baltic Sea area in Northern Europe. Repeated BoNT type C/D botulism outbreaks have occurred, but it remains unclear whether this is the sole and primary cause of mortality. Thiamine deficiency has also been suggested as a causal or contributing factor. With this study, we aimed to investigate gross and microscopic pathology in Herring gulls from affected breeding sites in Sweden in search of contributing diseases. Herring gulls from Iceland served as controls. Necropsies and histopathology were performed on 75 birds, of which 12 showed signs of disease at the time of necropsy. Parasites of various classes and tissues were commonly observed independent of host age, e.g. oesophageal capillariosis and nematode infection in the proventriculus and gizzard with severe inflammation, air sac larid pentastomes and bursal trematodiasis in pre-fledglings. Gross and microscopic findings are described. Notably, amyloidosis was diagnosed in 93 and 33% of the adult birds from Sweden and Iceland, respectively ( p<0.001), with more pronounced deposits in Swedish birds ( p<0.001). Gastrointestinal deposits were observed in the walls of arteries or arterioles, and occasionally in villi near the mucosal surface. Amyloid was identified within the intestinal lumen in one severely affected gull suggesting the possibility of oral seeding and the existence of a primed state as previously described in some mammals and chickens. This could speculatively explain the high occurrence and previously reported rapid onset of amyloidosis upon inflammation or captivity in Herring gulls. Amyloid-induced malabsorbtion is also a possibility. The Herring gull SAA/AA protein sequence was shown to be highly conserved but differed at the N-terminus from other avian species.
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| 20. |
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| 21. |
- Jansson, Sven-Arne, et al.
(författare)
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Life-years lost due to asthma
- 2019
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Ingår i: European Respiratory Journal. - Sheffield : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 54:Suppl. 63
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Jansson, Sven-Arne, et al.
(författare)
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Subjects with well-controlled asthma have similar health-related quality of life as subjects without asthma
- 2016
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 120, s. 64-69
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The burden of asthma and rhinitis on health-related quality of life (HRQL) among adults has been assessed mainly in studies of patients seeking health-care, while population-based studies are relatively scarce. The objective of this study was to investigate HRQL among subjects with asthma and rhinitis derived from a random population sample and to identify factors related to impairment of HRQL.METHODS: A randomly selected cohort was invited to participate in a postal questionnaire survey. Of those who responded, a stratified sample of 1016 subjects was invited to clinical examinations and interviews, and 737 subjects in ages 21-86 years participated. Of these, 646 completed HRQL questions. HRQL was assessed with the generic SF-36 Health Survey.RESULTS: The physical score was lower among subjects with asthma vs. subjects without asthma (p < 0.001). No significant difference was found in the mental score. Subjects with well-controlled asthma had higher physical score compared to subjects with partly and un-controlled asthma (p = 0.002). Actually, subjects with well-controlled asthma had similar physical HRQL as subjects without asthma. Asthmatics who were current smokers had lower physical score compared to those who were non-smokers (p = 0.021). No significant differences in physical or mental scores were found between subjects with and without rhinitis. Subjects with both asthma and rhinitis had lower physical score compared to subjects without these conditions (p < 0.001), but subjects with asthma alone had even worse physical score.CONCLUSIONS: The physical score was significantly lower in asthmatics compared to subjects without asthma. Importantly, non-smoking and well-controlled asthmatics have similar HRQL compared to subjects without asthma. Thus, subjects with asthma should be supported to achieve and maintain good asthma control and if they smoke, be offered smoking cessation as means to improve their HRQL.
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| 23. |
- Karlsson, Jenny, et al.
(författare)
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Aberrant epigenetic regulation in clear cell sarcoma of the kidney featuring distinct DNA hypermethylation and EZH2 overexpression.
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:10, s. 36-11127
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Tidskriftsartikel (refereegranskat)abstract
- The global methylation profile and the mutational status of 633 specific epigenetic regulators were analyzed in the pediatric tumor clear cell sarcoma of the kidney (CCSK). Methylation array analyses of 30 CCSKs revealed CCSK tumor DNA to be globally hypermethylated compared to Wilms tumor, normal fetal kidney, and adult kidney. The aberrant methylation pattern of CCSKs was associated with activation of genes involved in embryonic processes and with silencing of genes linked to normal kidney function. No epigenetic regulator was recurrently mutated in our cohort, but a mutation in the key epigenetic regulator EZH2 was discovered in one case. EZH2 mRNA was significantly higher in CCSK compared to Wilms tumor and normal kidney, and the EZH2 protein was strongly expressed in more than 90 % of CCSK tumor cells in 9/9 tumors analyzed. This was in striking contrast to the lack of EZH2 protein expression in Wilms tumor stromal elements, indicating that EZH2 could be explored further as a diagnostic marker and a potential drug target for CCSK.
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| 24. |
- Karlsson, Jenny, et al.
(författare)
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Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:7, s. 944-950
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge to personalized oncology is that driver mutations vary among cancer cells inhabiting the same tumor. Whether this reflects principally disparate patterns of Darwinian evolution in different tumor regions has remained unexplored1–5. We mapped the prevalence of genetically distinct clones over 250 regions in 54 childhood cancers. This showed that primary tumors can simultaneously follow up to four evolutionary trajectories over different anatomic areas. The most common pattern consists of subclones with very few mutations confined to a single tumor region. The second most common is a stable coexistence, over vast areas, of clones characterized by changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a clone with driver mutations or structural chromosome rearrangements emerges through a clonal sweep to dominate an anatomical region. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Death from disease was limited to tumors exhibiting the two last, most dynamic patterns.
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| 25. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 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
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 26. |
- 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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| 27. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 28. |
- Ravi, Naveen, et al.
(författare)
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Identification of targetable lesions in anaplastic thyroid cancer by genome profiling
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Anaplastic thyroid cancer (ATC) is a rare and extremely malignant tumor with no available cure. The genetic landscape of this malignancy has not yet been fully explored. In this study, we performed whole exome sequencing and the RNA-sequencing of fourteen cases of ATC to delineate copy number changes, fusion gene events, and somatic mutations. A high frequency of genomic amplifications was seen, including 29% of cases having amplification of CCNE1 and 9% of CDK6; these events may be targetable by cyclin dependent kinase (CDK) inhibition. Furthermore, 9% harbored amplification of TWIST1, which is also a potentially targetable lesion. A total of 21 fusion genes in five cases were seen, none of which were recurrent. Frequent mutations included TP53 (55%), the TERT promoter (36%), and ATM (27%). Analyses of mutational signatures showed an involvement of processes that are associated with normal aging, defective DNA mismatch repair, activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity, failure of DNA double-strand break repair, and tobacco exposure. Taken together, our results shed new light on the tumorigenesis of ATC and show that a relatively large proportion (36%) of ATCs harbor genetic events that make them candidates for novel therapeutic approaches. When considering that ATC today has a mortality rate of close to 100%, this is highly relevant from a clinical perspective.
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| 29. |
- Räisänen, Petri, et al.
(författare)
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Male sex, younger age and smoking contribute to low participating rate in an epidemiological study of asthma and respiratory symptoms
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: High participation rate is warranted in order to ensure the validity in epidemiological study results. However, participation rates in population based studies have declined during the last decades.Aim: To evaluate the causes and potential effects of non-response in a large population based survey about asthma and respiratory symptoms in Northern Sweden.Methods: In 2016 a random sample of 12000 adults in ages 20-79 were invited to a postal questionnaire survey about asthma, rhinitis and respiratory symptoms. Three reminders were sent out. A random sample of 500 non-responders was identified for a telephone interview.Results: The participation rate in the initial mailing was 40.6%, and 9.0%, 4.9%, and 2.6% in the subsequent reminders; in total 57.1% (n=6854) participated. Of the 500 non-responders, 320 were possible to reach and 272 participated in the interviews. The prevalence of respiratory symptoms did not differ significantly between responders and non-responders. Male sex, younger age, and smoking were associated with both late and non-response. Even if more subjects with asthma or allergic rhinitis were late and non-responders the prevalence estimates of these conditions were not substantially affected. However, 11.7% of participants and 18.0% of non-responders were smokers (p <0.001). Reasons for non-participation were mainly lack of time and having forgotten to answer.Conclusion: With a response rate of 57.1%, our prevalence estimates of asthma and respiratory symptom were not biased while smoking was underestimated in this Swedish population.
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| 30. |
- Selberg, Stina, et al.
(författare)
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Asthma control and acute health care visits among young adults with asthma : A population‐based study
- 2019
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Ingår i: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648. ; 75:12, s. 3525-3534
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo study asthma control and acute health care visits among young adults with asthma.BackgroundDespite the access to effective treatment and nursing interventions, poor asthma control is still common among individuals with asthma. However, studies describing clinical characteristics among young adults with asthma are rare.DesignA population‐based cohort study.MethodsIn 2015, as a part of the OLIN pediatric cohort I (recruited in 1996 at age 7‐8yr), N=2291 young adults (27‐28 yr) completed a postal questionnaire survey including questions on asthma and respiratory symptoms. Of these, N=280 (12%) were identified as having current asthma and were further studied.ResultsOf those with current asthma, women reported respiratory symptoms and smoking to a greater extent than men. Approximately one‐fourth had uncontrolled asthma and acute health care visits due to asthma was reported by 15% of women and 8% of men. Uncontrolled asthma was associated with smoking, lower educational level, use of reliever treatment most days and acute health care visits. Acute health care visits due to asthma were associated with periodic use of regular controller treatment also after adjustment for uncontrolled asthma.ConclusionThe result indicate poor adherence to asthma treatment which may lead to decreased asthma control and acute health care visits.ImpactMost young adults with asthma are diagnosed and treated in primary care, ideally in a team with a nurse. The main findings highlight the need for evidenced‐based nursing interventions, contributing to a more efficient asthma management in primary care.
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| 31. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 32. |
- Volgsten, Helena, 1959-, et al.
(författare)
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Longitudinal study of emotional experiences, grief and depressive symptoms in women and men after miscarriage
- 2018
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Ingår i: Midwifery. - : Elsevier. - 0266-6138 .- 1532-3099. ; 64, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Although miscarriage is common and affects up to 20 % of pregnant women, little is known about these couples’ short term and long term experiences after miscarriage.The aim of the present study was to study emotional experience, grief and depressive symptoms in women and men,one week and four months after miscarriage. Research design /setting:Women, (n=103), and their male partner (n=78), were recruited at the gynecological clinic after miscarriage. Control women were recruitedfrom the general population.Three validated questionnaires concerning psychological wellbeing and mental health, RIMS, PGS and MADRS-S were answered by the participants one week and four months after the miscarriage. Findings: It was shown that for women, the emotional experiences of miscarriage, grief and depressive symptoms were more pronounced than for their male partners. Grief and depressive symptoms were reduced with time, which was not the case for the emotional experiences of miscarriage. Previous children was favorable for emotional experience while previous miscarriage or infertility treatment made the emotional experience worse. Conclusion: Grief and depressive symptoms is reducedover time while emotional experiences such as isolation, loss of baby and a devastating event persist for longer time than four months. Lack of previous children, previous miscarriageand infertility diagnosis could increase negative emotional experiencesafter miscarriage, this was especially pronounced for grief reaction.The questionnaires could be used both clinically and in research to understand the emotional experiences after miscarriage.
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| 33. |
- Volgsten, Helena, 1959-, et al.
(författare)
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Women's experiences of miscarriage related to diagnosis, duration, and type of treatment
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:12, s. 1491-1498
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Women with miscarriage experience several negative emotional feelings such as grief, isolation, coping, and despair. However, less is known about how the type of treatment and diagnosis of miscarriage influence the emotional experience.MATERIAL AND METHODS: The present study was a randomized prospective longitudinal cohort study, in which women with spontaneous miscarriage (n = 35), and women with missed miscarriage (n = 67), were included to answer 3 validated questionnaires: Revised Impact of Miscarriage Scale, Perinatal Grief Scale, and Montgomery and Åsberg Depression Rating Scale, concerning experience of miscarriage, psychological well-being, and mental health 1 week and 4 months after finalized treatment.RESULTS: There was no difference between the 2 diagnosis groups in feelings as measured by Revised Impact of Miscarriage Scale, Montgomery and Åsberg Depression Rating Scale, and Perinatal Grief Scale 1 week after the miscarriage. However, the psychological well-being improved significantly 4 months after the miscarriage. Separated by treatment, women treated with misoprostol alone had more depressive symptoms than women treated with misoprostol and subsequent vacuum aspiration.CONCLUSIONS: It can be concluded that diagnosis of miscarriage had limited influence on the experiences of miscarriage, but shorter duration of treatment with misoprostol and subsequent vacuum aspiration resulted in fewer depressive symptoms.
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| 34. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 35. |
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