Publication: Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Issued Date
2021-12-01
Resource Type
ISSN
20411723
Other identifier(s)
2-s2.0-85117731180
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.12, No.1 (2021)
Suggested Citation
María Gordillo-Marañón, Magdalena Zwierzyna, Pimphen Charoen, Fotios Drenos, Sandesh Chopade, Tina Shah, Jorgen Engmann, Nishi Chaturvedi, Olia Papacosta, Goya Wannamethee, Andrew Wong, Reecha Sofat, Mika Kivimaki, Jackie F. Price, Alun D. Hughes, Tom R. Gaunt, Deborah A. Lawlor, Anna Gaulton, Aroon D. Hingorani, Amand F. Schmidt, Chris Finan Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics. Nature Communications. Vol.12, No.1 (2021). doi:10.1038/s41467-021-25731-z Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/75911
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Title
Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Author(s)
María Gordillo-Marañón
Magdalena Zwierzyna
Pimphen Charoen
Fotios Drenos
Sandesh Chopade
Tina Shah
Jorgen Engmann
Nishi Chaturvedi
Olia Papacosta
Goya Wannamethee
Andrew Wong
Reecha Sofat
Mika Kivimaki
Jackie F. Price
Alun D. Hughes
Tom R. Gaunt
Deborah A. Lawlor
Anna Gaulton
Aroon D. Hingorani
Amand F. Schmidt
Chris Finan
Magdalena Zwierzyna
Pimphen Charoen
Fotios Drenos
Sandesh Chopade
Tina Shah
Jorgen Engmann
Nishi Chaturvedi
Olia Papacosta
Goya Wannamethee
Andrew Wong
Reecha Sofat
Mika Kivimaki
Jackie F. Price
Alun D. Hughes
Tom R. Gaunt
Deborah A. Lawlor
Anna Gaulton
Aroon D. Hingorani
Amand F. Schmidt
Chris Finan
Other Contributor(s)
Faculty of Tropical Medicine, Mahidol University
Bristol Medical School
NIHR Bristol Biomedical Research Centre
Edinburgh Medical School
British Heart Foundation
University Medical Center Utrecht
European Bioinformatics Institute
University College London
University of Bristol
Brunel University London
Mahidol University
Bristol Medical School
NIHR Bristol Biomedical Research Centre
Edinburgh Medical School
British Heart Foundation
University Medical Center Utrecht
European Bioinformatics Institute
University College London
University of Bristol
Brunel University London
Mahidol University
Abstract
Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target’s expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process.