Search: onr:"swepub:oai:lup.lub.lu.se:9e0ee81d-7c6f-4ee7-be38-a8fab21a874c" >
Mapping genetic det...
Mapping genetic determinants of 184 circulating proteins in 26,494 individuals to connect proteins and diseases
-
- Macdonald-Dunlop, Erin (author)
- University of Edinburgh
-
- Klaric, Lucija (author)
- Western General Hospital
-
- Folkersen, Lasse (author)
- Danish National Genome Center
-
show more...
-
- Timmers, Paul R H J (author)
- University of Edinburgh
-
- Gustafsson, Stefan (author)
- Uppsala University
-
- Hua Zhao, Jing (author)
- University of Cambridge
-
- Eriksson, Niclas (author)
- Uppsala University
-
- Richmond, Anne (author)
- Western General Hospital
-
- Enroth, Stefan (author)
- Uppsala University
-
- Mattsson-Carlgren, Niklas (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital
-
- Zhernakova, Daria V (author)
- University Medical Center Groningen
-
- Magnusson, Martin (author)
- Lund 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
-
- Smith, J. Gustav (author)
- University of Gothenburg,Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Heart Failure and Mechanical Support,Forskargrupper vid Lunds universitet,Molecular Epidemiology and Cardiology,Cardiovascular Epigenetics,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,Sahlgrenska University Hospital,Skåne University Hospital
-
- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
-
show less...
-
(creator_code:org_t)
- Cold Spring Harbor Laboratory, 2021
- English 27 s.
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://www.medrxiv....
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- We performed the largest genome-wide meta-analysis (GWAMA) (Max N=26,494) of the levels of 184 cardiovascular-related plasma protein levels to date and reported 592 independent loci (pQTL) associated with the level of at least one protein (1308 significant associations, median 6 per protein). We estimated that only between 8-37% of testable pQTL overlap with established expression quantitative trait loci (eQTL) using multiple methods, while 132 out of 1064 lead variants show evidence for transcription factor binding, and found that 75% of our pQTL are known DNA methylation QTL. We highlight the variation in genetic architecture between proteins and that proteins share genetic architecture with cardiometabolic complex traits. Using cis-instrument Mendelian randomisation (MR), we infer causal relationships for 11 proteins, recapitulating the previously reported relationship between PCSK9 and LDL cholesterol, replicating previous pQTL MR findings and discovering 16 causal relationships between protein levels and disease. Our MR results highlight IL2-RA as a candidate for drug repurposing for Crohn’s Disease as well as 2 novel therapeutic targets: IL-27 (Crohn’s disease) and TNFRSF14 (Inflammatory bowel disease, Multiple sclerosis and Ulcerative colitis). We have demonstrated the discoveries possible using our pQTL and highlight the potential of this work as a resource for genetic epidemiology.
Subject headings
- 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)
Publication and Content Type
- ovr (subject category)
- vet (subject category)
To the university's database
- By the author/editor
-
Macdonald-Dunlop ...
-
Klaric, Lucija
-
Folkersen, Lasse
-
Timmers, Paul R ...
-
Gustafsson, Stef ...
-
Hua Zhao, Jing
-
show more...
-
Eriksson, Niclas
-
Richmond, Anne
-
Enroth, Stefan
-
Mattsson-Carlgre ...
-
Zhernakova, Dari ...
-
Magnusson, Marti ...
-
Smith, J. Gustav
-
Hansson, Oskar
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Medical Genetics
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cardiac and Card ...
- By the university
-
Lund University