Plasma Protein Profile Associated With a Family History of Early-Onset Coronary Heart Disease
(2025) In Circulation: Genomic and Precision Medicine 18(6). p.005220-005220- Abstract
BACKGROUND: – Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization. METHODS: – Data on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved... (More)
BACKGROUND: – Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization. METHODS: – Data on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved from national registers. Linear associations between family history and proteins were adjusted for age, sex, and study site. Statistical interactions between proteins and family history for the association between proteins and the coronary atherosclerotic burden were also studied. Mendelian randomization for causal associations between proteins and CHD was performed with genome-wide association study summary data from UKB-PPP (UK Biobank Pharma Proteomics Project), CARDIoGRAMplusC4D, and FinnGen. RESULTS: – Of 4251 subjects, family history of early-onset CHD was present in 9.5%. Thirty-eight proteins, with biological features of inflammation, lipid metabolism, and vascular function, were associated with family history using a false discovery rate of 0.05. The strongest associations were observed with cathepsin D, paraoxonase 3, renin andfollistatin, neither of which was attenuated by adjusting for cardiovascular risk factors. Eighteen proteins were statistical interactors with family history in the association between each protein and the coronary atherosclerotic burden, most notably the LDL (low-density lipoprotein) receptor, transferrin receptor protein 1, and PECAM1 (platelet endothelial cell adhesion molecule 1). In 2-sample Mendelian randomization, a novel association was found for follistatin and myocardial infarction, and previous associations for PCSK9 (proprotein convertase subtilisin/kexin type 9) and PECAM1 were repeated. CONCLUSIONS: – These findings highlight new potential mechanisms for heritable and general atherosclerosis.
(Less)
- author
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cardiovascular diseases, coronary artery disease, follistatin, Mendelian randomization analysis, myocardial infarction
- in
- Circulation: Genomic and Precision Medicine
- volume
- 18
- issue
- 6
- pages
- 005220 - 005220
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:105025138549
- pmid:41200820
- ISSN
- 2574-8300
- DOI
- 10.1161/CIRCGEN.124.005220
- language
- English
- LU publication?
- yes
- id
- 9d97860c-9b6c-4ab4-a439-1116079ac2c6
- date added to LUP
- 2026-02-12 16:28:21
- date last changed
- 2026-02-13 03:00:05
@article{9d97860c-9b6c-4ab4-a439-1116079ac2c6,
abstract = {{<p>BACKGROUND: – Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization. METHODS: – Data on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved from national registers. Linear associations between family history and proteins were adjusted for age, sex, and study site. Statistical interactions between proteins and family history for the association between proteins and the coronary atherosclerotic burden were also studied. Mendelian randomization for causal associations between proteins and CHD was performed with genome-wide association study summary data from UKB-PPP (UK Biobank Pharma Proteomics Project), CARDIoGRAMplusC4D, and FinnGen. RESULTS: – Of 4251 subjects, family history of early-onset CHD was present in 9.5%. Thirty-eight proteins, with biological features of inflammation, lipid metabolism, and vascular function, were associated with family history using a false discovery rate of 0.05. The strongest associations were observed with cathepsin D, paraoxonase 3, renin andfollistatin, neither of which was attenuated by adjusting for cardiovascular risk factors. Eighteen proteins were statistical interactors with family history in the association between each protein and the coronary atherosclerotic burden, most notably the LDL (low-density lipoprotein) receptor, transferrin receptor protein 1, and PECAM1 (platelet endothelial cell adhesion molecule 1). In 2-sample Mendelian randomization, a novel association was found for follistatin and myocardial infarction, and previous associations for PCSK9 (proprotein convertase subtilisin/kexin type 9) and PECAM1 were repeated. CONCLUSIONS: – These findings highlight new potential mechanisms for heritable and general atherosclerosis.</p>}},
author = {{Wahrenberg, Agnes and Lind, Lars and Åberg, Natan and Häbel, Henrike and Ström, Marika and Mälarstig, Anders and Magnusson, Patrik K.E. and Kuja-Halkola, Ralf and Bergström, Göran and Engström, Gunnar and Hagström, Emil and Jernberg, Tomas and Söderberg, Stefan and Östgren, Carl Johan and Svensson, Per}},
issn = {{2574-8300}},
keywords = {{cardiovascular diseases; coronary artery disease; follistatin; Mendelian randomization analysis; myocardial infarction}},
language = {{eng}},
number = {{6}},
pages = {{005220--005220}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Circulation: Genomic and Precision Medicine}},
title = {{Plasma Protein Profile Associated With a Family History of Early-Onset Coronary Heart Disease}},
url = {{http://dx.doi.org/10.1161/CIRCGEN.124.005220}},
doi = {{10.1161/CIRCGEN.124.005220}},
volume = {{18}},
year = {{2025}},
}