Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development.

Humans Venous Thromboembolism / genetics Proteome / genetics Genome-Wide Association Study / methods Mendelian Randomization Analysis Bayes Theorem Serpin E2 / genetics Blood Proteins / genetics Polymorphism, Single Nucleotide Extracellular Matrix Proteins / genetics

Journal

Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 27 04 2023
accepted: 23 07 2023
revised: 19 06 2023
medline: 28 11 2023
pubmed: 4 8 2023
entrez: 3 8 2023
Statut: ppublish

Résumé

Genome-wide association studies (GWAS) have identified numerous risk loci for venous thromboembolism (VTE), but it is challenging to decipher the underlying mechanisms. We employed an integrative analytical pipeline to transform genetic associations to identify novel plasma proteins for VTE. Proteome-wide association studies (PWAS) were determined by functional summary-based imputation leveraging data from a genome-wide association analysis (14,429 VTE patients, 267,037 controls), blood proteomes (1348 cases), followed by Mendelian randomization, Bayesian colocalization, protein-protein interaction, and pathway enrichment analysis. Twenty genetically regulated circulating protein abundances (F2, F11, ABO, PLCG2, LRP4, PLEK, KLKB1, PROC, KNG1, THBS2, SERPINA1, RARRES2, CEL, GP6, SERPINE2, SERPINA10, OBP2B, EFEMP1, F5, and MSR1) were associated with VTE. Of these 13 proteins demonstrated Mendelian randomized correlations. Six proteins (F2, F11, PLEK, SERPINA1, RARRES2, and SERPINE2) had strong support in colocalization analysis. Utilizing multidimensional data, this study suggests PLEK, SERPINA1, and SERPINE2 as compelling proteins that may provide key hints for future research and possible diagnostic and therapeutic targets for VTE.

Identifiants

DOI: 10.1038/s10038-023-01186-6 PMID: 37537391 PMC: PMC10678328
pubmed: 37537391
doi: 10.1038/s10038-023-01186-6
pii: 10.1038/s10038-023-01186-6
pmc: PMC10678328
doi:

Substances chimiques

Proteome 0
Serpin E2 0
Blood Proteins 0
EFEMP1 protein, human 0
Extracellular Matrix Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

805-812

Subventions

Organisme : Chinese Academy of Medical Sciences (CAMS)
ID : 2021-I2M-1-061
Organisme : Beijing Nova Program
ID : Z211100002121057
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82100065
Organisme : China-Japan Friendship Hospital Youth Science and Technology Excellence Project
ID : ZRJY2021-QM12

Informations de copyright

© 2023. The Author(s).

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Auteurs

Haobo Li (H)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
ORCID: 0000-0002-1882-5831

Zhu Zhang (Z)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. zhuperfectlife@126.com.

Yuting Qiu (Y)

Capital Medical University, Beijing, China.

Haoyi Weng (H)

WeGene, Shenzhen, China; Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha, China.

Shuai Yuan (S)

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Yunxia Zhang (Y)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.

Yu Zhang (Y)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Capital Medical University, Beijing, China.

Linfeng Xi (L)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Capital Medical University, Beijing, China.

Feiya Xu (F)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Capital Medical University, Beijing, China.

Xiaofan Ji (X)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Risheng Hao (R)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Capital Medical University, Beijing, China.

Peiran Yang (P)

State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases, Beijing, China.

Gang Chen (G)

WeGene, Shenzhen, China; Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha, China.

Xianbo Zuo (X)

Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.

Zhenguo Zhai (Z)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. zhaizhenguo2011@126.com.
ORCID: 0000-0002-7096-8792

Chen Wang (C)

National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China. wangchen@pumc.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Proteome-wide mendelian randomization...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thromboembolie › Thromboembolisme veineux › Proteome-wide mendelian randomization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéome › Proteome-wide mendelian randomization...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Proteome-wide mendelian randomization...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Proteome-wide mendelian randomization...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Théorème de Bayes › Proteome-wide mendelian randomization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Serpine E2 › Proteome-wide mendelian randomization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Proteome-wide mendelian randomization...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Proteome-wide mendelian randomization...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Proteome-wide mendelian randomization...