Search: onr:"swepub:oai:gup.ub.gu.se/297596" >
Genomic and drug ta...
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Folkersen, LasseDanish National Genome Center
(author)
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-10-16
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Springer Science and Business Media LLC,2020
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/297596
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https://gup.ub.gu.se/publication/297596URI
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https://doi.org/10.1038/s42255-020-00287-2DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-424065URI
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https://lup.lub.lu.se/record/9a451a80-186c-48e3-984d-ad6861a35aa6URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:145007830URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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De tre första författarna delar förstaförfattarskapetDe tre sista författarna delar sistaförfattarskapet
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Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Gustafsson, StefanUppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:lu)extLU-1433
(author)
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Wang, QinUniversity of Oulu
(author)
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Hansen, Daniel HvidbergIntomics A/S
(author)
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Hedman, Åsa KKarolinska Institutet,Karolinska Institute,Pfizer Limited, UK
(author)
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Schork, AndrewTranslational Genomics Research Institute (TGen)
(author)
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Page, KarenPfizer Inc. US
(author)
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Zhernakova, Daria VUniversity of Groningen
(author)
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Wu, YangUniversity of Queensland
(author)
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Peters, JamesImperial College London,University of Cambridge
(author)
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Eriksson, Niclas,1978-Uppsala University,Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)nieri103
(author)
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Bergen, Sarah EKarolinska Institutet,Karolinska Institute
(author)
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Boutin, Thibaud SUniversity of Edinburgh
(author)
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Bretherick, Andrew DSCALLOP consortium
(author)
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Enroth, Stefan,1976-Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Gyllensten(Swepub:uu)stenr451
(author)
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Kalnapenkis, AnetteSCALLOP consortium
(author)
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Gådin, Jesper RKarolinska Institutet
(author)
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Suur, Bianca EKarolinska Institutet
(author)
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Chen, YanKarolinska Institutet,Karolinska Institute
(author)
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Matic, LjubicaKarolinska Institutet
(author)
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Gale, Jeremy DSCALLOP consortium
(author)
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Lee, JulieSCALLOP consortium
(author)
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Zhang, WeidongSCALLOP consortium
(author)
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Quazi, AmiraSCALLOP consortium
(author)
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Ala-Korpela, MikaSCALLOP consortium
(author)
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Choi, Seung HoanSCALLOP consortium
(author)
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Claringbould, AnniqueSCALLOP consortium
(author)
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Danesh, JohnSCALLOP consortium
(author)
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Davey Smith, GeorgeSCALLOP consortium
(author)
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de Masi, FedericoSCALLOP consortium
(author)
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Elmståhl, SölveLund University,Lunds universitet,Geriatrik,Forskargrupper vid Lunds universitet,Geriatrics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)smi-sel
(author)
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Engström, GunnarLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)smi-gen
(author)
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Fauman, Eric
(author)
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Fernandez, CelineLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medk-cfe
(author)
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Franke, Lude
(author)
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Franks, Paul WLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf
(author)
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Giedraitis, VilmantasUppsala universitet,Geriatrik(Swepub:uu)vigie517
(author)
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Haley, Chris
(author)
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Hamsten, AndersKarolinska Institutet
(author)
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Ingason, Andres
(author)
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Johansson, ÅsaUppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)asjoh108
(author)
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Joshi, Peter K
(author)
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Lind, LarsUppsala universitet,Klinisk epidemiologi(Swepub:uu)larslind
(author)
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Lindgren, Cecilia MLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Cardiovascular Research - Hypertension,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)medf-mma
(author)
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Lubitz, Steven
(author)
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Palmer, Tom
(author)
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Macdonald-Dunlop, Erin
(author)
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Nilsson, Peter MLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-pni
(author)
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Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ome
(author)
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Michaëlsson, Karl,1959-Uppsala universitet,Ortopedi(Swepub:uu)karlmich
(author)
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Morris, Andrew P
(author)
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Mägi, Reedik
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Nagle, Michael W
(author)
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Nilsson, Peter M
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Nilsson, JanLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-jni
(author)
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Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor
(author)
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Polasek, Ozren
(author)
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Prins, Bram
(author)
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Pålsson, Erik
(author)
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Qi, Ting
(author)
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Sjögren, MarketaLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - hypertoni,Genetic and Molecular Epidemiology,Lund University Research Groups,Cardiovascular Research - Hypertension,Skåne University Hospital(Swepub:lu)endo-msj
(author)
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Sundström, Johan,Professor,1971-Uppsala universitet,Klinisk epidemiologi,The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia(Swepub:uu)johasund
(author)
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Surendran, Praveen
(author)
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Võsa, Urmo
(author)
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Werge, Thomas
(author)
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Wernersson, Rasmus
(author)
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Westra, Harm-Jan
(author)
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Yang, Jian
(author)
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Zhernakova, Alexandra
(author)
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Ärnlöv, JohanKarolinska Institutet
(author)
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Fu, Jingyuan
(author)
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Smith, GustavLund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine(Swepub:lu)med-gvs
(author)
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Esko, Tõnu
(author)
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Hayward, Caroline
(author)
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Gyllensten, UlfUppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik(Swepub:uu)ulfgyll
(author)
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Landén, Mikael,1966Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlandt
(author)
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Siegbahn, Agneta,1947-Uppsala universitet,Klinisk kemi(Swepub:uu)agsie424
(author)
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Wilson, James F
(author)
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Wallentin, Lars,1943-Uppsala University,Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)larswall
(author)
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Butterworth, Adam S
(author)
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Holmes, Michael V
(author)
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Ingelsson, Erik
(author)
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Mälarstig, AndersKarolinska Institutet
(author)
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Danish National Genome CenterScience for Life Laboratory, SciLifeLab
(creator_code:org_t)
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In:Nature metabolism: Springer Science and Business Media LLC2:10, s. 1135-11482522-5812
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Folkersen, Lasse
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Gustafsson, Stef ...
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Wang, Qin
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Hansen, Daniel H ...
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Hedman, Åsa K
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Schork, Andrew
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Page, Karen
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Zhernakova, Dari ...
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Wu, Yang
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Peters, James
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Eriksson, Niclas ...
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Bergen, Sarah E
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Boutin, Thibaud ...
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Bretherick, Andr ...
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Enroth, Stefan, ...
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Kalnapenkis, Ane ...
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Gådin, Jesper R
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Suur, Bianca E
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Chen, Yan
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Matic, Ljubica
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Gale, Jeremy D
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Lee, Julie
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Zhang, Weidong
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Quazi, Amira
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Ala-Korpela, Mik ...
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Choi, Seung Hoan
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Claringbould, An ...
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Danesh, John
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Davey Smith, Geo ...
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de Masi, Federic ...
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Elmståhl, Sölve
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Engström, Gunnar
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Fauman, Eric
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Fernandez, Celin ...
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Franke, Lude
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Franks, Paul W
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Giedraitis, Vilm ...
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Haley, Chris
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Hamsten, Anders
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Ingason, Andres
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Johansson, Åsa
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Joshi, Peter K
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Lind, Lars
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Lindgren, Cecili ...
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Lubitz, Steven
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Palmer, Tom
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Macdonald-Dunlop ...
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Nilsson, Peter M
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Melander, Olle
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Michaëlsson, Kar ...
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Morris, Andrew P
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Mägi, Reedik
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Nagle, Michael W
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Nilsson, Jan
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Orho-Melander, M ...
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Polasek, Ozren
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Prins, Bram
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Pålsson, Erik
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Qi, Ting
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Sjögren, Marketa
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Sundström, Johan ...
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Surendran, Prave ...
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Võsa, Urmo
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Werge, Thomas
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Wernersson, Rasm ...
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Westra, Harm-Jan
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Yang, Jian
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Zhernakova, Alex ...
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Ärnlöv, Johan
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Fu, Jingyuan
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Smith, Gustav
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Esko, Tõnu
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Hayward, Carolin ...
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Gyllensten, Ulf
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Landén, Mikael, ...
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Siegbahn, Agneta ...
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Wilson, James F
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Wallentin, Lars, ...
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Butterworth, Ada ...
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Holmes, Michael ...
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Ingelsson, Erik
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Mälarstig, Ander ...
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University of Gothenburg
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Uppsala University
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