Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

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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

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2020-10-16
Springer Science and Business Media LLC,2020

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LIBRIS-ID:oai:gup.ub.gu.se/297596
https://gup.ub.gu.se/publication/297596URI
https://doi.org/10.1038/s42255-020-00287-2DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-424065URI
https://lup.lub.lu.se/record/9a451a80-186c-48e3-984d-ad6861a35aa6URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:145007830URI

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Language:English

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Subject category:art swepub-publicationtype

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De tre första författarna delar förstaförfattarskapetDe tre sista författarna delar sistaförfattarskapet
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

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Psykiatri hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Psychiatry hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng

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Eriksson, Niclas,1978-Uppsala University,Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)nieri103 (author)
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Boutin, Thibaud SUniversity of Edinburgh (author)
Bretherick, Andrew DSCALLOP consortium (author)
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Gådin, Jesper RKarolinska Institutet (author)
Suur, Bianca EKarolinska Institutet (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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In:Nature metabolism: Springer Science and Business Media LLC2:10, s. 1135-11482522-5812

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By the author/editor: Folkersen, Lasse; Gustafsson, Stef ...; Wang, Qin; Hansen, Daniel H ...; Hedman, Åsa K; Schork, Andrew; show more...; Page, Karen; Zhernakova, Dari ...; Wu, Yang; Peters, James; Eriksson, Niclas ...; Bergen, Sarah E; Boutin, Thibaud ...; Bretherick, Andr ...; Enroth, Stefan, ...; Kalnapenkis, Ane ...; Gådin, Jesper R; Suur, Bianca E; Chen, Yan; Matic, Ljubica; Gale, Jeremy D; Lee, Julie; Zhang, Weidong; Quazi, Amira; Ala-Korpela, Mik ...; Choi, Seung Hoan; Claringbould, An ...; Danesh, John; Davey Smith, Geo ...; de Masi, Federic ...; Elmståhl, Sölve; Engström, Gunnar; Fauman, Eric; Fernandez, Celin ...; Franke, Lude; Franks, Paul W; Giedraitis, Vilm ...; Haley, Chris; Hamsten, Anders; Ingason, Andres; Johansson, Åsa; Joshi, Peter K; Lind, Lars; Lindgren, Cecili ...; Lubitz, Steven; Palmer, Tom; Macdonald-Dunlop ...; Nilsson, Peter M; Melander, Olle; Michaëlsson, Kar ...; Morris, Andrew P; Mägi, Reedik; Nagle, Michael W; Nilsson, Jan; Orho-Melander, M ...; Polasek, Ozren; Prins, Bram; Pålsson, Erik; Qi, Ting; Sjögren, Marketa; Sundström, Johan ...; Surendran, Prave ...; Võsa, Urmo; Werge, Thomas; Wernersson, Rasm ...; Westra, Harm-Jan; Yang, Jian; Zhernakova, Alex ...; Ärnlöv, Johan; Fu, Jingyuan; Smith, Gustav; Esko, Tõnu; Hayward, Carolin ...; Gyllensten, Ulf; Landén, Mikael, ...; Siegbahn, Agneta ...; Wilson, James F; Wallentin, Lars, ...; Butterworth, Ada ...; Holmes, Michael ...; Ingelsson, Erik; Mälarstig, Ander ...; show less...

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