| 1. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 2. |
- Silventoinen, Karri, et al.
(författare)
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The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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| 3. |
- Shi, Liu, et al.
(författare)
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Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.
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| 4. |
- Shi, Liu, et al.
(författare)
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Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.
- 2019
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 15:11, s. 1478-1488
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Tidskriftsartikel (refereegranskat)abstract
- Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.4001 plasma proteins were measured in two groups of participants (discovery group=516, replication group=365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid.A panel of proteins (n=44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve=0.78) and the replication group (area under the curve=0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization.The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.
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| 5. |
- Bi, Z, et al.
(författare)
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Identical genotypes of community-associated MRSA (ST59) and livestock-associated MRSA (ST9) in humans and pigs in rural China
- 2018
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Ingår i: Zoonoses and Public Health. - : Wiley-VCH Verlagsgesellschaft. - 1863-1959 .- 1863-2378. ; 65:3, s. 367-371
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the prevalence of MRSA in samples taken in households, with and without backyard pigs in villages in a rural area of Shandong Province, China. Community-associated MRSA and livestock-associated MRSA, belonging to ST59 and ST9, respectively, were identified in both humans and pigs. The genotypic and phenotypic comparison of isolates indicates that bidirectional transmission of MRSA has occurred between humans and pigs in the villages.
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| 6. |
- Burke, Kristin E., et al.
(författare)
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Identification of Menopausal and Reproductive Risk Factors for Microscopic Colitis-Results From the Nurses' Health Study
- 2018
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Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 155:6, s. 1764-1775
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized.METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals.RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis.CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.
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| 7. |
- Cars, Otto, et al.
(författare)
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Building bridges to operationalise one health : A Sino-Swedish collaboration to tackle antibiotic resistance
- 2016
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Ingår i: One Health. - : Elsevier. - 2352-7714. ; 2, s. 139-143
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is a complex global health challenge. The recent Global Action Plan on antimicrobial resistance highlights the importance of adopting One Health approaches that can cross traditional disciplinary boundaries. We report on the early experiences of a multisectoral Sino-Swedish research project that aims to address gaps in our current knowledge and seeks to improve the situation through system-wide interventions. Our research project is investigating antibiotic use and resistance in a rural area of China through a combination of epidemiological, health systems and laboratory investigations. We reflect here on the challenges inherent in conducting long distance cross-disciplinary collaborations, having now completed data and sample collection for a baseline situation analysis. In particular, we recognise the importance of investing in aspects such as effective communication, shared conceptual frameworks and leadership. We suggest that our experiences will be instructive to others planning to develop similar international One Health collaborations.
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| 8. |
- Drobin, Kimi, et al.
(författare)
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Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
- 2019
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1078-0998 .- 1536-4844. ; 25:2, s. 306-316
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.
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| 9. |
- Liu, Po-Hong, et al.
(författare)
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Dietary Gluten Intake and Risk of Microscopic Colitis Among US Women without Celiac Disease : A Prospective Cohort Study
- 2019
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Ingår i: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 114:1, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Microscopic colitis is a common cause of chronic watery diarrhea among the elderly. Although the prevalence of celiac disease appears to be higher in patients with microscopic colitis, the relationship between dietary gluten intake and risk of microscopic colitis among individuals without celiac disease has not been explored.METHODS: We conducted a prospective study of 160,744 US women without celiac disease enrolled in the Nurses' Health Study (NHS) and the NHSII. Dietary gluten intake was estimated using validated food frequency questionnaires every 4 years. Microscopic colitis was confirmed through medical records review. We used Cox proportional hazard modeling to estimate the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI).RESULTS: We documented 219 incident cases of microscopic colitis over more than 20 years of follow-up encompassing 3,716,718 person-years (crude incidence rate: 5.9/100,000 person-years) in NHS and NHSII. Dietary gluten intake was not associated with risk of microscopic colitis (Ptrend = 0.88). Compared to individuals in the lowest quintile of energy-adjusted gluten intake, the adjusted HR of microscopic colitis was 1.18 (95% CI: 0.77-1.78) for the middle quintile and 1.03 (95% CI: 0.67-1.58) for the highest quintile. Additional adjustment for primary dietary sources of gluten including refined and whole grains did not materially alter the effect estimates (All Ptrend ≥ 0.69). The null association did not differ according to lymphocytic or collagenous subtypes (Pheterogeneity = 0.72) and was not modified by age, smoking status, or body mass index (All Pinteraction ≥ 0.17).CONCLUSION: Dietary gluten intake during adulthood was not associated with risk of microscopic colitis among women without celiac disease.
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| 10. |
- Liu, Po-Hong, et al.
(författare)
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Obesity and Weight Gain Since Early Adulthood Are Associated With a Lower Risk of Microscopic Colitis
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:12, s. 2523-2532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Obesity promotes intestinal inflammation and might contribute to the pathogenesis of inflammatory bowel disease. We examined the association between obesity and risk of microscopic colitis in a prospective cohort study.METHODS: We collected data from 192,101 women enrolled in the Nurses' Health Study (NHS) (from 1986 through 2014) or the NHSII (from 1991 through 2015). Anthropomorphic and lifestyle information were self-reported biennially. Obesity was defined using body mass index (BMI). Microscopic colitis was confirmed by review of medical records. We used Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Among the participants in the NHS and NHSII, we confirmed 244 cases of microscopic colitis during 4,223,868 person-years of follow-up evaluation. Higher BMI was associated inversely with risk of microscopic colitis (Ptrend < .001). Compared with women with BMIs ranging from 18.5 to 20.9 kg/m(2), the aHRs were 0.61 (95% CI, 0.41-0.91) for overweight women (BMI, 2529.9 kg/m(2)) and 0.50 (95% CI, 0.32-0.79) for obese women (BMI >= 30 kg/m(2)). The aHR for each 5-kg/m(2) increase in BMI was 0.79 (95% CI, 0.69-0.90). Weight gain since early adulthood (age, 18 y) also was associated inversely with risk of microscopic colitis (Ptrend = .001). The aHR for each 10-kg weight gain since early adulthood was 0.85 (95% CI, 0.77-0.94). The associations were not modified by age, cohort, physical activity, or smoking status (all Pinteraction >= .26).CONCLUSIONS: Unlike many other immune- and metabolic-related disorders, obesity and weight gain since early adulthood were associated with a lower risk of microscopic colitis, based on an analysis of participants in the NHS and NHSII.
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