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- 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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- 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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- Aktas, A., et al.
(författare)
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Elastic J/psi production at HERA
- 2006
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 46:3, s. 585-603
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Tidskriftsartikel (refereegranskat)abstract
- Cross sections for elastic production of J/psi mesons in photoproduction and electroproduction are measured in electron proton collisions at HERA using an integrated luminosity of 55 pb(-1). Results are presented for photon virtualities Q(2) up to 80 GeV2. The dependence on the photon-proton centre of mass energy W-gamma p is analysed in the range 40 <= W-gamma p <= 305 GeV in photoproduction and 40 <= W-gamma p <= 160 GeV in electroproduction. The W-gamma p dependences of the cross sections do not change significantly with Q(2) and can be described by models based on perturbative QCD. Within such models, the data show a high sensitivity to the gluon density of the proton in the domain of low Bjorken x and low Q(2). Differential cross sections d sigma/dt, where t is the squared four-momentum transfer at the proton vertex, are measured in the range vertical bar t vertical bar < 1.2 GeV2 as functions of W-gamma p and Q(2). Effective Pomeron trajectories are determined for photoproduction and electroproduction. The J/psi production and decay angular distributions are consistent with s-channel helicity conservation. The ratio of the cross sections for longitudinally and transversely polarised photons is measured as a function of Q(2) and is found to be described by perturbative QCD based models.
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- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 9. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 10. |
- Aaron, F. D., et al.
(författare)
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A search for excited neutrinos in e(-) p collisions at HERA
- 2008
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 663:5, s. 382-389
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Tidskriftsartikel (refereegranskat)abstract
- A search for first generation excited neutrinos is performed using the full e(-) p data sample collected by the HI experiment at HERA at a centre-of-mass energy of 319 GeV, corresponding to a total luminosity of 184 pb(-1). The electroweak decays of excited neutrinos nu* -> nu gamma, v* -> nu Z and nu* -> eW with subsequent hadronic or leptonic decays of the W and Z bosons are considered. No evidence for excited neutrino production is found. Mass dependent exclusion limits on nu* production cross sections and on the ratio of the coupling to the compositeness scale f/boolean AND are derived within gauge mediated models. A limit on f/boolean AND A, independent of the relative couplings to the SU(2) and U(1) gauge bosons, is also determined. These limits extend the excluded region to higher masses than has been possible in previous excited neutrino searches. (c) 2008 Elsevier B.V. All rights reserved.
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