| 1. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Chen, Dongfeng, et al.
(författare)
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Glioma Cell Proliferation Controlled by ERK Activity-Dependent Surface Expression of PDGFRA.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Increased PDGFRA signaling is an essential pathogenic factor in many subtypes of gliomas. In this context the cell surface expression of PDGFRA is an important determinant of ligand sensing in the glioma microenvironment. However, the regulation of spatial distribution of PDGFRA in glioma cells remains poorly characterized. Here, we report that cell surface PDGFRA expression in gliomas is negatively regulated by an ERK-dependent mechanism, resulting in reduced proliferation of glioma cells. Glioma tumor tissues and their corresponding cell lines were isolated from 14 patients and analyzed by single-cell imaging and flow cytometry. In both cell lines and their corresponding tumor samples, glioma cell proliferation correlated with the extent of surface expression of PDGFRA. High levels of surface PDGFRA also correlated to high tubulin expression in glioma tumor tissue in vivo. In glioma cell lines, surface PDGFRA declined following treatment with inhibitors of tubulin, actin and dynamin. Screening of a panel of small molecule compounds identified the MEK inhibitor U0126 as a potent inhibitor of surface PDGFRA expression. Importantly, U0126 inhibited surface expression in a reversible, dose- and time-dependent manner, without affecting general PDGFRA expression. Treatment with U0126 resulted in reduced co-localization between PDGFRA and intracellular trafficking molecules e.g. clathrin, RAB11 and early endosomal antigen-1, in parallel with enhanced co-localization between PDGFRA and the Golgi cisternae maker, Giantin, suggesting a deviation of PDGFRA from the endosomal trafficking and recycling compartment, to the Golgi network. Furthermore, U0126 treatment in glioma cells induced an initial inhibition of ERK1/2 phosphorylation, followed by up-regulated ERK1/2 phosphorylation concomitant with diminished surface expression of PDGFRA. Finally, down-regulation of surface PDGFRA expression by U0126 is concordant with reduced glioma cell proliferation. These findings suggest that manipulation of spatial expression of PDGFRA can potentially be used to combat gliomas.
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| 4. |
- Duan, Haiping, et al.
(författare)
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Heritability of Age-Related Hearing Loss in Middle-Aged and Elderly Chinese : A Population-Based Twin Study
- 2019
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Ingår i: Ear and Hearing. - 0196-0202 .- 1538-4667. ; 40:2, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The heritability of age-related hearing loss has been studied mostly in developed countries. The authors aimed to estimate the heritability of better ear hearing level (BEHL), defined as hearing level of the better ear at a given frequency, and pure-tone averages at the middle (0.5, 1.0, and 2.0 kHz) and high (4.0, 8.0, and 12.5 kHz) frequencies among middle-aged and elderly Chinese twins, and to explore their genetic correlations.Design: This population-based twin study included 226 monozygotic and 132 dizygotic twin-pairs and 1 triplet (age range, 33 to 80 years; mean age, 51.55 years). Pure-tone air-conducted hearing thresholds in each ear were measured at the frequencies of 0.5, 1.0, 2.0, 4.0, 8.0, and 12.5 kHz with a diagnostic audiometer. Univariate and multivariate twin models were fitted to evaluate heritability and genetic correlations.Results: Our data showed a reverse J-shaped pattern of BEHLs at six frequencies by age and sex. Univariate analysis showed that the heritability of BEHLs at the frequencies between 2.0 and 12.5 kHz ranged from 47.08 to 54.20%, but the heritability at the frequencies of 0.5 and 1.0 kHz was 1.65% and 18.68%, respectively. The heritability of pure-tone average at the middle and high frequencies was 34.77% and 43.26%, respectively. Multivariate analysis showed significant genetic correlations among BEHLs at all six frequencies, with the correlation coefficients ranging from 0.48 to 0.83 at middle frequencies, and from 0.46 to 0.75 at high frequencies.Conclusions: This population-based twin study suggests that genetic factors are associated with age-related hearing loss at middle and high frequencies among middle-aged and elderly Chinese.
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| 5. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 6. |
- 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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| 7. |
- Ma, Zaifei, et al.
(författare)
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A Facile Method to Enhance Photovoltaic Performance of Benzodithiophene-Isoindigo Polymers by Inserting Bithiophene Spacer
- 2014
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Ingår i: Advanced Energy Materials. - : Wiley. - 1614-6840 .- 1614-6832. ; 4:6, s. Art. no. 1301455-
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Tidskriftsartikel (refereegranskat)abstract
- This study describes the synthesis and characterization of four polymers based on benzo[1,2-b:4,5-b']dithiophene (BDT) and isoindigo with zero, one, two, and three thiophene spacer groups. Results have demonstrated that the use of bithiophene as a spacer unit improves the geometry of the polymer chain, making it planar, and hence, potentially enhanced π- π stacking occurs. Due to favorable interaction of the polymer chains, enhanced absorption coefficient, and optimal morphology, PBDT-BTI, which possesses bithiophene as a spacer, revealed high current and fill factor leading to a power conversion efficiency of 7.3% in devices, making this polymer the best performing isoindigo-based material in polymer solar cells (PSCs). Also, PBDT-BTI could still maintain efficiency of over 6% with the active layer thickness of 270 nm, making it a potential candidate for a material in printed PSCs. These results demonstrate that the use of thiophene spacers in D-A polymers could be an important design strategy to produce high-performance PSCs.
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| 8. |
- Nikpay, Majid, et al.
(författare)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 9. |
- Raposeiras-Roubin, Sergio, et al.
(författare)
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Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome : The BleeMACS score
- 2018
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 254, s. 10-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome(ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients.Methods: The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI.Results: Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts.Conclusions: The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding.
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| 10. |
- Silventoinen, Karri, et al.
(författare)
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Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
- 2017
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Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Tidskriftsartikel (refereegranskat)abstract
- Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
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| 11. |
- Silventoinen, Karri, et al.
(författare)
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Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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| 12. |
- Silventoinen, Karri, et al.
(författare)
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Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts
- 2022
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
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| 13. |
- 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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| 14. |
- Sun, Wenjun, 1989, et al.
(författare)
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An alternating D-A1-D-A2 copolymer containing two electron-deficient moieties for efficient polymer solar cells
- 2013
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 1:37, s. 11141-11144
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Tidskriftsartikel (refereegranskat)abstract
- Unlike normal donor-acceptor (D-A) polymers containing only one electron-deficient segment in their repeating unit, the incorporation of two electron-deficient moieties with different absorption behaviors, forming a D-A1-D-A2 internal structure in the alternating copolymer, showed a broader absorption spectrum than its constituent parts and enhanced photovoltaic performance. This work is anticipated to open the door to the design of new low bandgap polymers with a broader absorption range for efficient polymer solar cells.
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| 15. |
- Sun, Yingyu, et al.
(författare)
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A glioma classification scheme based on coexpression modules of EGFR and PDGFRA
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 111:9, s. 3538-3543
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that key signaling pathways of glioma genesis might enable the molecular classification of gliomas. Gene coexpression modules around epidermal growth factor receptor (EGFR) (EM, 29 genes) or platelet derived growth factor receptor A (PDGFRA) (PM, 40 genes) in gliomas were identified. Based on EM and PM expression signatures, nonnegative matrix factorization reproducibly clustered 1,369 adult diffuse gliomas WHO grades II-IV from four independent databases generated in three continents, into the subtypes (EM, PM and EMlowPMlow gliomas) in a morphology-independent manner. Besides their distinct patterns of genomic alterations, EM gliomas were associated with higher age at diagnosis, poorer prognosis, and stronger expression of neural stem cell and astrogenesis genes. Both PM and EMlowPMlow gliomas were associated with younger age at diagnosis and better prognosis. PM gliomas were enriched in the expression of oligodendrogenesis genes, whereas EMlowPMlow gliomas were enriched in the signatures of mature neurons and oligodendrocytes. The EM/PM-based molecular classification scheme is applicable to adult low-grade and high-grade diffuse gliomas, and outperforms existing classification schemes in assigning diffuse gliomas to subtypes with distinct transcriptomic and genomic profiles. The majority of the EM/PM classifiers, including regulators of glial fate decisions, have not been extensively studied in glioma biology. Subsets of these classifiers were coexpressed in mouse glial precursor cells, and frequently amplified or lost in an EM/PM glioma subtypespecific manner, resulting in somatic copy number alteration-dependent gene expression that contributes to EM/PM signatures in glioma samples. EM/PM-based molecular classification provides a molecular diagnostic framework to expedite the search for new glioma therapeutic targets.
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| 16. |
- Tang, Shi, et al.
(författare)
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Fluorescent carbon dots from birch leaves for sustainable electroluminescent devices
- 2023
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Ingår i: Green Chemistry. - : Royal Society of Chemistry. - 1463-9262 .- 1463-9270. ; 25:23, s. 9884-9895
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Tidskriftsartikel (refereegranskat)abstract
- The shift from depleting petroleum compounds to regenerating biomass as the raw material for organic semiconductors is a prerequisite if organic electronics is to become truly sustainable. Here, we report on a one-pot solvothermal synthesis of a biomass-based carbon dot (bio-CD) fluorescent semiconductor, using birch leaves as the sole raw material. These bio-CDs are highly soluble in ethanol (45 g L-1), and deliver deep-red and narrowband emission (peak wavelength = 675 nm, full width at half maximum, FWHM = 28 nm) at a high photoluminescence quantum yield of 26% in ethanol solution. Systematic structural characterization shows that molecular pheophytin a is the single fluorophore, and that this fluorophore is localized in the bulk of the bio-CD away from its polar surface. The functionality of the birch-leaf-derived bio-CDs in sustainable organic electronics is demonstrated by its employment as the printable emitter in a light-emitting electrochemical cell, which delivers narrowband deep-red luminance of 110 cd m-2, with a FWHM of 29 nm, at an external quantum efficiency of 0.29%. This study thus reveals a promising avenue for the functional benign synthesis and the practical solution-based implementation of narrowband bio-CDs in sustainable optoelectronic technologies.
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| 17. |
- Wen, Wanqing, et al.
(författare)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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| 18. |
- Zhang, Y., et al.
(författare)
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Dysregulation of autophagy acts as a pathogenic mechanism of non-alcoholic fatty liver disease (NAFLD) induced by common environmental pollutants
- 2021
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513. ; 217
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) has been the most common chronic liver disease in the world, including the developing countries. NAFLD is metabolic disease with significant lipid deposition in the hepatocytes of the liver, which is usually associated with oxidative stress, inflammation and fibrogenesis, and insulin resistance. Progressive NAFLD can develop into non-alcoholic steatohepatitis (NASH) or hepatocellular carcinoma. The current evidence proposes that environmental pollutants promote development and progression of NAFLD, and autophagy plays a vital role but is multifactorial affected in NAFLD. In this review, we analyzed on the regulations of common environmental pollutants on autophagy in NAFLD. To clarify the involved roles of autophagy, we discussed the dysregulation of autophagy by environmental pollutants in adipose tissue and gut, and their interactions with liver, as well as epigenetic regulation on autophagy by environmental pollutants. Furthermore, protective roles of potential therapeutic treatments on the multiple-hits of autophagy in NAFLD were descripted.
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