| 31. |
- Flannick, Jason, et al.
(författare)
-
Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
|
|
| 32. |
- Freitag, Daniel F., et al.
(författare)
-
Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
-
Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
-
Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
|
|
| 33. |
- Fuchsberger, Christian, et al.
(författare)
-
The genetic architecture of type 2 diabetes
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
|
|
| 34. |
- Geng, Huifang, et al.
(författare)
-
Controlled synthesis of highly stable lead-free bismuth halide perovskite nanocrystals : tructures and photophysics
- 2023
-
Ingår i: SCIENCE CHINA Materials. - : Springer Science and Business Media LLC. - 2095-8226 .- 2199-4501. ; 66:5, s. 2079-2089
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, cesium bismuth halide perovskites have emerged as potential substitutes to their counterparts, cesium lead halide perovskites, owing to their low toxicity. However, the photophysics of cesium-bismuth halides nanocrystals (NCs) have not yet been fully rationalized because their structures remain highly debated. The ultraviolet-visible (UV-vis) absorption along with other photophysical properties such as the nature and lifetime of the excited states vary considerably across the previous reports. Here, we successfully synthesize pure Cs3BiBr6 and Cs3Bi2Br9 NCs via a modified hot-injection method, where the structure can be easily controlled by tuning the reaction temperature. The UV-vis absorption spectrum of the pure Cs3Bi2Br9 NCs features two characteristic peaks originating from the absorption of the first exciton and second exciton, respectively, which ultimately clarifies the debate in the previous reports. Using femtosecond transient absorption spectroscopy, we systematically investigate the excited state dynamics of the Cs3Bi2Br9 NCs and reveal that the photoexcited carriers undergo a self-trapping process within 3 ps after excitation. More intriguingly, the Cs3Bi2Br9 NCs prepared by this method show much better photostability than those prepared by the ligand-assisted reprecipitation process. Photodetectors based on these Cs3Bi2Br9 NCs show a sensitive light response, demonstrating the definite potential for breakthrough optoelectronic applications. [Figure not available: see fulltext.].
|
|
| 35. |
- Ghosh, Supriya, et al.
(författare)
-
Slower Auger Recombination in 12-Faceted Dodecahedron CsPbBr3 Nanocrystals
- 2023
-
Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 14:4, s. 1066-1072
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past two decades, intensive research efforts have been devoted to suppressions of Auger recombination in metal-chalcogenide and perovskite nanocrystals (PNCs) for the application of photovoltaics and light emitting devices (LEDs). Here, we have explored dodecahedron cesium lead bromide perovskite nanocrystals (DNCs), which show slower Auger recombination time compared to hexahedron nanocrystals (HNCs). We investigate many-body interactions that are manifested under high excitation flux density in both NCs using ultrafast spectroscopic pump-probe measurements. We demonstrate that the Auger recombination rate due to multiexciton recombinations are lower in DNCs than in HNCs. At low and intermediate excitation density, the majority of carriers recombine through biexcitonic recombination. However, at high excitation density (>1018 cm-3) a higher number of many-body Auger process dominates over biexcitonic recombination. Compared to HNCs, high PLQY and slower Auger recombinations in DNCs are likely to be significant for the fabrication of highly efficient perovskite-based photonics and LEDs.
|
|
| 36. |
- Hansen, Violeta, 1979, et al.
(författare)
-
Naturally occurring radionuclides assessment in the Arctic
- 2023
-
Ingår i: The XIX conference of the Nordic Society for Radiation Protection, held at Malmö Live, Malmö, Sweden, June 5-9, 2023. - https://nsfs.org/?lang=en : The Nordic Society for Radiation Protection (NSFS).
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Naturally occurring radionuclides (NORs), primarily 210Po, accumulates in seafood, marine, and terrestrial mammals, which are an important part of the traditional Arctic diet. Arctic seafood plays an important role in the worldwide seafood industry. NORs were measured in glaciers from Svalbard, the Arctic Ocean, surface seawater and sediments from Norwegian marine areas, seabirds from Greenland, seafood and marine mammals from the Nordic region, Faroe Islands, Greenland, and Canada, terrestrial mammals from Greenland, and lake sediments in northernmost Finland. Outdoor 222Rn was measured in Finland, Canada, and Norway and atmospheric 210Pb, 212Pb, and 7Be were measured in Norway, Sweden, Finland, Iceland, and Canada. Deposited 210Pb and 7Be were measured in Sweden and Finland. Glaciers and marine sediment results show oil and gas, coal combustion, and ore mining as anthropogenic sources. NORs are long-range transported via atmospheric and oceanic currents in the Arctic. 210Pb has a long atmospheric residence time, especially in winter. 228Ra activities in the Transpolar Drift approximately doubled between 2007 and 2015, indicating that climate-driven changes may be increasing the release of shelf-derived elements to the open Arctic Ocean. Results showed no effect of climate change on 210Pb deposition in sediments in Lake Kevojarvi in northernmost Finland. 210Po is the major contributor to the annual effective dose via seafood and marine and terrestrial mammal consumption in the Arctic population, far exceeding dose contributions from 137Cs, 226Ra, 228Ra, and 210Pb. 210Po absorbed dose rates to studied biota are several orders of magnitude lower than the recommended dose rate screening value of 10 µGy h-1. NORs atmospheric results follow an annual cycle, which is mainly driven by seasonal weather and climate changes. Understanding the sources and associated doses from NORs is necessary to assess risks and public perception of risks, support science-based decision-making, and policy development engaging public and Indigenous peoples.
|
|
| 37. |
- Hong, Li, et al.
(författare)
-
Thiocyanate-Mediated Dimensionality Transformation of Low- Dimensional Perovskites for Photovoltaics
- 2022
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 34:14, s. 6331-6338
-
Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional (2D) hybrid perovskite solar cells have induced widespread research interest owing to their higher stability as compared to three-dimensional (3D) analogues. The photovoltaic performance, however, is still limited. Here, we report a perovskite film dominated by 3D components that are modulated by formamidinium thiocyanate in the 2D PEA(2)FA(3)Pb(4)I(13) perovskite composition. We demonstrate that a dimensionality transformation from a 2D/3D to predominantly 3D perovskite phase in the presence of SCN-based treatment enhances the optical absorption in visible and near-infrared regions. As a result, the power conversion efficiency improved 4.5 times with respect to the control to above 14%. The unencapsulated cell exhibited excellent moisture stability during the shelf lifetime measurement over 70 days under ambient conditions.
|
|
| 38. |
- Jhun, Mina-A, et al.
(författare)
-
A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
|
|
| 39. |
- Justice, Anne E., et al.
(författare)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
|
|
| 40. |
- Kanoni, Stavroula, et al.
(författare)
-
Analysis with the exome array identifies multiple new independent variants in lipid loci
- 2016
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:18, s. 4094-4106
-
Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
|
|
