| 1. |
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 5. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 6. |
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| 7. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 8. |
- Aaltonen, T., et al.
(författare)
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Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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| 9. |
- Aaltonen, T., et al.
(författare)
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Tevatron Run II combination of the effective leptonic electroweak mixing angle
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:11
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Tidskriftsartikel (refereegranskat)abstract
- Drell-Yan lepton pairs produced in the process p (p) over bar -> l(+)l(-) + X through an intermediate gamma*/Z boson have an asymmetry in their angular distribution related to the spontaneous symmetry breaking of the electroweak force and the associated mixing of its neutral gauge bosons. The CDF and D0 experiments have measured the effective-leptonic electroweak mixing parameter sin(2) theta(lept)(eff) using electron and muon pairs selected from the full Tevatron proton-antiproton data sets collected in 2001-2011, corresponding to 9-10 fb(-1) of integrated luminosity. The combination of these measurements yields the most precise result from hadron colliders, sin(2)theta(lept)(eff) = 0.23148 +/- 0.00033. This result is consistent with, and approaches in precision, the best measurements from electron-positron colliders. The standard model inference of the on-shell electroweak mixing parameter sin(2) theta(W), or equivalently the W-boson mass M-W, using the ZFITTER software package yields sin(2) theta(W) = 0.22324 +/- 0.00033 or equivalently, M-W = 80.367 +/- 0.017 GeV/c(2).
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| 10. |
- Aaltonen, T., et al.
(författare)
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Combination of CDF and D0 W-Boson mass measurements
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:5, s. 052018-
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Tidskriftsartikel (refereegranskat)abstract
- We summarize and combine direct measurements of the mass of the W boson in root s = 1.96 TeV proton-antiproton collision data collected by CDF and D0 experiments at the Fermilab Tevatron Collider. Earlier measurements from CDF and D0 are combined with the two latest, more precise measurements: a CDF measurement in the electron and muon channels using data corresponding to 2.2 fb(-1) of integrated luminosity, and a D0 measurement in the electron channel using data corresponding to 4.3 fb(-1) of integrated luminosity. The resulting Tevatron average for the mass of the W boson is M-W = 80387 +/- 16 MeV. Including measurements obtained in electron-positron collisions at LEP yields the most precise value of M-W = 80385 +/- 15 MeV.
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| 11. |
- Aaltonen, T., et al.
(författare)
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Combination of measurements of the top-quark pair production cross section from the Tevatron Collider
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:7
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Tidskriftsartikel (refereegranskat)abstract
- We combine six measurements of the inclusive top-quark pair (t(sic)) production cross section (sigma(t)(sic)) from data collected with the CDF and D0 detectors at the Fermilab Tevatron with proton-antiproton collisions at root s = 1.96 TeV. The data correspond to integrated luminosities of up to 8.8 fb(-1). We obtain a value of sigma tt = 7.60 +/- 0.41 pb for a top-quark mass of m(t) = 172.5 GeV. The contributions to the uncertainty are 0.20 pb from statistical sources, 0.29 pb from systematic sources, and 0.21 pb from the uncertainty on the integrated luminosity. The result is in good agreement with the standard model expectation of 7.35(-0.33)(+0.28) pb at next-to-next-to-leading order and next-to-next-to leading logarithms in perturbative QCD.
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| 12. |
- Aaltonen, T., et al.
(författare)
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Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 120:4
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Tidskriftsartikel (refereegranskat)abstract
- The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of root s = 1.96 TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is A(FB)(t (t) over bar) = 0.128 +/- 0.025. The combined inclusive and differential asymmetries are consistent with recent standard model predictions.
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| 13. |
- Aaltonen, T., et al.
(författare)
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Evidence for a Particle Produced in Association with Weak Bosons and Decaying to a Bottom-Antibottom Quark Pair in Higgs Boson Searches at the Tevatron
- 2012
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 109:7, s. 071804-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for the associated production of a Higgs boson with a W or Z boson and subsequent decay of the Higgs boson to a bottom-antibottom quark pair. The data, originating from Fermilab Tevatron p (p) over bar collisions at root s = 1.96 TeV, correspond to integrated luminosities of up to 9.7 fb(-1). The searches are conducted for a Higgs boson with mass in the range 100-150 GeV/c(2). We observe an excess of events in the data compared with the background predictions, which is most significant in the mass range between 120 and 135 GeV/c(2). The largest local significance is 3.3 standard deviations, corresponding to a global significance of 3.1 standard deviations. We interpret this as evidence for the presence of a new particle consistent with the standard model Higgs boson, which is produced in association with a weak vector boson and decays to a bottom-antibottom quark pair.
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| 14. |
- Aaltonen, T., et al.
(författare)
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Observation of s-Channel Production of Single Top Quarks at the Tevatron
- 2014
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:23
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Tidskriftsartikel (refereegranskat)abstract
- We report the first observation of single-top-quark production in the s channel through the combination of the CDF and D0 measurements of the cross section in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The measured cross section is sigma(s) = 1.29(-0.24)(+0.26) pb. The probability of observing a statistical fluctuation of the background to a cross section of the observed size or larger is 1.8 x 10(-10), corresponding to a significance of 6.3 standard deviations for the presence of an s-channel contribution to the production of single-top quarks.
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| 15. |
- Aaltonen, T., et al.
(författare)
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Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element V-tb
- 2015
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 115:15
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Tidskriftsartikel (refereegranskat)abstract
- We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb(-1) per experiment. The t-channel cross section is measured to be sigma(t) = 2.25(-0.31)(+0.29) pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s + t channel cross section measurement resulting in sigma(s+t) = 3.30(-0.40)(+0.52) pb, without assuming the standard model value for the ratio sigma(s)/sigma(t). The resulting value of the magnitude of the top-to-bottom quark coupling is vertical bar V-tb vertical bar = 1.02(-0.05)(+0.06), corresponding to vertical bar V-tb vertical bar > 0.92 at the 95% C. L.
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| 16. |
- Aaltonen, T., et al.
(författare)
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Tevatron Constraints on Models of the Higgs Boson with Exotic Spin and Parity Using Decays to Bottom-Antibottom Quark Pairs
- 2015
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 114:15
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Tidskriftsartikel (refereegranskat)abstract
- Combined constraints from the CDF and D0 Collaborations on models of the Higgs boson with exotic spin J and parity P are presented and compared with results obtained assuming the standard model value J(P) = 0(+). Both collaborations analyzed approximately 10 fb(-1) of proton-antiproton collisions with a center-of-mass energy of 1.96 TeV collected at the Fermilab Tevatron. Two models predicting exotic Higgs bosons with J(P) = 0(-) and J(P) = 2(+) are tested. The kinematic properties of exotic Higgs boson production in association with a vector boson differ from those predicted for the standard model Higgs boson. Upper limits at the 95% credibility level on the production rates of the exotic Higgs bosons, expressed as fractions of the standard model Higgs boson production rate, are set at 0.36 for both the J(P) = 0(-) hypothesis and the J(P) = 2(+) hypothesis. If the production rate times the branching ratio to a bottom-antibottom pair is the same as that predicted for the standard model Higgs boson, then the exotic bosons are excluded with significances of 5.0 standard deviations and 4.9 standard deviations for the J(P) = 0(-) and J(P) = 2(+) hypotheses, respectively.
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| 17. |
- Aaltonen, T., et al.
(författare)
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Combination of CDF and D0 measurements of the W boson helicity in top quark decays
- 2012
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 85:7, s. 071106-
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Tidskriftsartikel (refereegranskat)abstract
- We report the combination of recent measurements of the helicity of the W boson from top quark decay by the CDF and D0 collaborations, based on data samples corresponding to integrated luminosities of 2.7-5.4 fb(-1) of p (p) over bar collisions collected during Run II of the Fermilab Tevatron collider. Combining measurements that simultaneously determine the fractions of W bosons with longitudinal (f(0)) and right-handed (f(+)) helicities, we find f(0) = 0.722 +/- 0.081[+/- 0.062(stat) +/- 0.052(syst)] and f(+) = -0.033 +/- 0.046[+/- 0.034(stat) +/- 0.031(syst)]. Combining measurements where one of the helicity fractions is fixed to the value expected in the standard model, we find f(0) = 0.682 +/- 0.057[+/- 0.035(stat) +/- 0.046(syst)] for fixed f(+) and f(+) = -0.015 +/- 0.035[+/- 0.018(stat) +/- 0.030(syst)] for fixed f(0). The results are consistent with standard model expectations.
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| 18. |
- Aaltonen, T., et al.
(författare)
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Higgs boson studies at the Tevatron
- 2013
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:5, s. 052014-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for the standard model Higgs boson with mass in the range 90-200 GeV/c(2) produced in the gluon-gluon fusion, WH, ZH, t (t) over barH, and vector boson fusion processes, and decaying in the H -> b (b) over bar, H -> W+W-, H -> ZZ, H -> tau(+)tau(-), and H -> gamma gamma modes. The data correspond to integrated luminosities of up to 10 fb(-1) and were collected at the Fermilab Tevatron in p (p) over bar collisions at root s = 1.96 TeV. The searches are also interpreted in the context of fermiophobic and fourth generation models. We observe a significant excess of events in the mass range between 115 and 140 GeV/c(2). The local significance corresponds to 3.0 standard deviations at m(H) = 125 GeV/c(2), consistent with the mass of the Higgs boson observed at the LHC, and we expect a local significance of 1.9 standard deviations. We separately combine searches for H -> b (b) over bar, H -> W+W-, H -> tau(+)tau(-), and H -> gamma gamma. The observed signal strengths in all channels are consistent with the presence of a standard model Higgs boson with a mass of 125 GeV/c(2).
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| 19. |
-
- 2019
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Tidskriftsartikel (refereegranskat)
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)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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| 24. |
- Abe, K., et al.
(författare)
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Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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| 25. |
- Groenen, M. A., et al.
(författare)
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Analyses of pig genomes provide insight into porcine demography and evolution
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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| 26. |
- Sugita, S., et al.
(författare)
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The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
- 2019
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Ingår i: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
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Tidskriftsartikel (refereegranskat)abstract
- Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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| 27. |
- Chauhan, G., et al.
(författare)
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Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p([BI]) = 9.38 x 10(-25); p([SSBI]) = 5.23 x 10(-14) for hypertension), smoking (p([BI]) = 4.4 x 10(-10); p([SSBI]) = 1.2 x 10(-4)), diabetes (p([BI]) = 1.7 x 10(-8); p([SSBI]) = 2.8 x 10(-3)), previous cardiovascular disease (p([BI]) = 1.0 x 10(-18); p([SSBI]) = 2.3 x 10(-7)), stroke (p([BI]) = 3.9 x 10(-69); p([SSBI]) = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p([BI]) = 1.43 x 10(-157); p([SSBI]) = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
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| 28. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 29. |
- Holl, Matthias, 1986, et al.
(författare)
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Border of the island of inversion: Unbound states in Ne-29
- 2022
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- The nucleus Ne-29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f(7/2) state, which would place Ne-29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne-29 is reported. The states were populated in Ne-30(p, pn) and Na-30(p, 2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing assignments for the observed states. The lowest lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant l = 3 component, giving first evidence for f(7/2) single particle strength in Ne-29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the SDPF-U-MIX interaction.
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| 30. |
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| 31. |
- Sakatani, N., et al.
(författare)
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Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
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Ingår i: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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| 32. |
- 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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| 33. |
- Kondo, Y., et al.
(författare)
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First observation of 28 O
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620:7976, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.
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| 34. |
- Revel, A., et al.
(författare)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Tidskriftsartikel (refereegranskat)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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| 35. |
- Wang, H., et al.
(författare)
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Intruder configurations in 29 Ne at the transition into the island of inversion: Detailed structure study of 28 Ne
- 2023
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 843
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Tidskriftsartikel (refereegranskat)abstract
- Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.
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| 36. |
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| 37. |
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| 38. |
- Browne, F., et al.
(författare)
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Pairing Forces Govern Population of Doubly Magic Ca-54 from Direct Reactions
- 2021
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 126:25
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Tidskriftsartikel (refereegranskat)abstract
- Direct proton-knockout reactions of Sc-55 at similar to 220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of Ca-54 were investigated through -ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological intemucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the Sc-55 ground state with states in Ca-54. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of Sc-55, valence proton removals populated predominantly the ground state of Ca-54. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.
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| 39. |
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| 40. |
- Doornenbal, P., et al.
(författare)
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Spectroscopy of 32Ne and the "œIsland of Inversion"
- 2009
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Ingår i: Physical Review Letters. - American Physical Society. - 0031-9007 .- 1079-7114. ; 103:3, s. 032501-1-032501-4
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first spectroscopic study of the N = 22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single γ-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV=u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV=u. This transition is assigned to the deexcitation of the first Jπ = 2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the ‘‘island of inversion’’ extends to at least N = 22 for the Ne isotopes.
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| 41. |
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| 42. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 43. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 48. |
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