| 1. |
- Chen, X., et al.
(author)
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A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
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Journal article (peer-reviewed)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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| 2. |
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| 3. |
- Franceschini, N., et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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| 4. |
- Lind, Lars, et al.
(author)
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Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
- 2017
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In: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 212-218
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Journal article (peer-reviewed)abstract
- Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.
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| 5. |
- Nilsson, Henrik, et al.
(author)
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Unipolar and bipolar operation of InAs/InSb nanowire heterostructure field-effect transistors
- 2011
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 110:6
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Journal article (peer-reviewed)abstract
- We present temperature dependent electrical measurements on n-type InAs/InSb nanowire heterostructure field-effect transistors. The barrier height of the heterostructure junction is determined to be 220 meV, indicating a broken bandgap alignment. A clear asymmetry is observed when applying a bias to either the InAs or the InSb side of the junction. Impact ionization and band-to-band tunneling is more pronounced when the large voltage drop occurs in the narrow bandgap InSb segment. For small negative gate-voltages, the InSb segment can be tuned toward p-type conduction, which induces a strong band-to-band tunneling across the heterostructucture junction. (c) 2011 American Institute of Physics. [doi: 10.1063/1.3633742]
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| 6. |
- Andric, Stefan, et al.
(author)
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Lateral III-V Nanowire MOSFETs in Low-Noise Amplifier Stages
- 2022
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In: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480. ; 70:2, s. 1284-1291
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Journal article (peer-reviewed)abstract
- Lateral III-V nanowire (NW) MOSFETs are a promising candidate for high-frequency electronics. However, their circuit performance is not yet assessed. Here, we integrate lateral nanowires (LNWs) in a circuit environment and characterize the transistors and amplifiers. MOSFETs are fabricated in a simple scheme with a dc transconductance of up to 1.3 mS/μm, ON-resistance down to 265 Ω · μ m, and cutoff frequencies up to 250 GHz, measured on the circuit level. The circuit model estimates 25% device parasitic capacitance increase due to back-end-of-line (BEOL) dielectric cladding. A low-noise amplifier input stage is designed with optimum network design for a noise matched input and an inductive peaking output. The input stage shows up to 4-dB gain and 2.5-dB noise figure (NF), at 60 GHz. Utilizing gate-length scaling in the circuit environment, the obtained normalized intrinsic gate capacitance value of 0.34-aF/nm gate length, per NW, corresponds well to the predicted theoretical value, demonstrating the circuit's ability to provide intrinsic device parameters. This is the first mm-wave validation of noise models for III-V LNW MOSFETs. The results demonstrate the potential for utilization of the technology platform for low-noise applications.
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| 7. |
- Andric, Stefan, et al.
(author)
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Performance, Analysis, and Modeling of III-V Vertical Nanowire MOSFETs on Si at Higher Voltages
- 2022
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In: IEEE Transactions on Electron Devices. - 0018-9383. ; 69:6, s. 3055-3055
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Journal article (peer-reviewed)abstract
- Heterostructure engineering in III-V vertical nanowire (VNW) MOSFETs enables tuning of transconductance and breakdown voltage. In this work, an InxGa 1−x As channel with a Ga-composition grading ( x= 1–0.4) in the channel and drain region, combined with field plate engineering, enables breakdown voltage above 2.5 V, while maintaining transconductance of about 1 mS/ μm , in VNW MOSFETs. The field plate consists of a vertically integrated SiO2 layer and a gate contact, which screens the electric field in the drain region, extending the device operating voltage. By scaling the field plate, a transconductance of 2 mS/ μm , alongside the breakdown voltage of 1.5 V, is obtained, demonstrating the benefit of field engineering in the drain. The scalability of the field plate and the gate is measured, showing an ON-resistance increase by 23 Ω⋅μm , and transconductance decrease by 5 μS/μm , per nm field plate length. This behavior is captured in a new and modified virtual source model, where device transmission and drain resistance are altered to capture the field plate scaling effect. The modeling is applied to nanowire (NW) devices with field plate lengths ranging from 5 to 115 nm, capturing accurately essential device performance parameters. Finally, a modified band-to-band (BTB) tunneling approach is used to accurately describe the device behavior above 1.5 V.
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| 8. |
- Arking, D. E., et al.
(author)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Journal article (peer-reviewed)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 9. |
- Artigas, MS, et al.
(author)
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Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8658-
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Journal article (peer-reviewed)abstract
- Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
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| 10. |
- Astromskas, Gvidas, et al.
(author)
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Temperature and frequency characterization of InAs nanowire and HfO2 interface using capacitance-voltage method
- 2011
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In: Microelectronic Engineering. - : Elsevier BV. - 1873-5568 .- 0167-9317. ; 88:4, s. 444-447
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Conference paper (peer-reviewed)abstract
- InAs/HfO2 nanowire capacitors using capacitance-voltage (CV) measurements are investigated in the range of 10 kHz to 10 MHz. The capacitors are based on vertical nanowire arrays that are coated with an 8 nm-thick HfO2 layer by atomic layer deposition. CV characteristics are measured at temperatures in the range between -140 and 40 degrees C and the CV characteristics for nanowires with different Sn and Se n-type doping levels are compared. The comparison of the data at various doping levels points towards large number of traps for highly doped samples, caused by the preferential dopant precursor incorporation at the nanowire surface. We also evaluate the frequency dispersion of the accumulation capacitance and determine values below 2% with weak temperature dependence, indicating the existence of border traps in these nanowire capacitors. (C) 2010 Elsevier B.V. All rights reserved.
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