Associations of genetic and infectious risk factors with coronary heart disease
Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and geno...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79742 |
| _version_ | 1811164928115998720 |
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| author | Flavia Hodel Zhi Ming Xu Christian Wandall Thorball Roxane de La Harpe Prunelle Letang-Mathieu Nicole Brenner Julia Butt Noemi Bender Tim Waterboer Pedro Manuel Marques-Vidal Peter Vollenweider Julien Vaucher Jacques Fellay |
| author_facet | Flavia Hodel Zhi Ming Xu Christian Wandall Thorball Roxane de La Harpe Prunelle Letang-Mathieu Nicole Brenner Julia Butt Noemi Bender Tim Waterboer Pedro Manuel Marques-Vidal Peter Vollenweider Julien Vaucher Jacques Fellay |
| author_sort | Flavia Hodel |
| collection | DOAJ |
| description | Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10–1.56, p=2.64 × 10−3) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08–2.45, p=1.99 × 10−2) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk. |
| first_indexed | 2024-04-10T15:29:11Z |
| format | Article |
| id | doaj.art-84fcbb8accc847e88781966660539632 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T15:29:11Z |
| publishDate | 2023-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-84fcbb8accc847e887819666605396322023-02-14T07:30:27ZengeLife Sciences Publications LtdeLife2050-084X2023-02-011210.7554/eLife.79742Associations of genetic and infectious risk factors with coronary heart diseaseFlavia Hodel0https://orcid.org/0000-0001-7331-7357Zhi Ming Xu1Christian Wandall Thorball2Roxane de La Harpe3Prunelle Letang-Mathieu4Nicole Brenner5https://orcid.org/0000-0002-7690-4925Julia Butt6Noemi Bender7https://orcid.org/0000-0003-2542-9949Tim Waterboer8Pedro Manuel Marques-Vidal9https://orcid.org/0000-0002-4548-8500Peter Vollenweider10Julien Vaucher11Jacques Fellay12https://orcid.org/0000-0002-8240-939XGlobal Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, SwitzerlandGlobal Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, SwitzerlandPrecision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandDepartment of Medicine, Internal medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandGlobal Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, SwitzerlandDivision of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, GermanyDivision of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, GermanyDivision of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, GermanyDivision of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, GermanyDepartment of Medicine, Internal medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandDepartment of Medicine, Internal medicine, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandPrecision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandGlobal Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandCoronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10–1.56, p=2.64 × 10−3) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08–2.45, p=1.99 × 10−2) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk.https://elifesciences.org/articles/79742coronary heart diseasepersistent infectionsinflammationhuman genomicsCox regression |
| spellingShingle | Flavia Hodel Zhi Ming Xu Christian Wandall Thorball Roxane de La Harpe Prunelle Letang-Mathieu Nicole Brenner Julia Butt Noemi Bender Tim Waterboer Pedro Manuel Marques-Vidal Peter Vollenweider Julien Vaucher Jacques Fellay Associations of genetic and infectious risk factors with coronary heart disease eLife coronary heart disease persistent infections inflammation human genomics Cox regression |
| title | Associations of genetic and infectious risk factors with coronary heart disease |
| title_full | Associations of genetic and infectious risk factors with coronary heart disease |
| title_fullStr | Associations of genetic and infectious risk factors with coronary heart disease |
| title_full_unstemmed | Associations of genetic and infectious risk factors with coronary heart disease |
| title_short | Associations of genetic and infectious risk factors with coronary heart disease |
| title_sort | associations of genetic and infectious risk factors with coronary heart disease |
| topic | coronary heart disease persistent infections inflammation human genomics Cox regression |
| url | https://elifesciences.org/articles/79742 |
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