Omics linking dietary pollutants to cardiovascular disease

Author
Affiliation
Tessa Schillemans

Karolinska Institutet

Published

September 12, 2022

Background:

Dietary exposure to persistent organic pollutants (POPs), including organochlorine compounds (OCs) and per- and polyfluoroalkyl substances (PFAS), is prevalent and may be linked to cardiovascular disease (CVD) development. To shed light on potential underlying mechanisms, we aimed to discover genetic, proteomic and metabolic features that link POP exposures with CVD risk using a “meet-in-the-middle” approach.

Method:

We used data from a nested case-control study on first incident myocardial infarction and stroke from the Swedish Mammography Cohort – Clinical (n=657). OCs, PFAS (LC-MS) and multiOmics (248 proteins from Olink CVDII, CVDIII and Metabolism panels; 9511 metabolic features from untargeted LCMS metabolomics and; 8110 gene variants selected from GWAS on POP exposures) were measured in baseline plasma. Omics features cross-sectionally associated with OCs and PFAS were selected using a random forest-based algorithm followed by partial Spearman correlation adjusting for confounders. POP-related omics features that also prospectively associated with cardiovascular outcomes were then selected using conditional logistic regression adjusted for confounders. Finally, associations of the selected omics features with POP exposures and CVD outcomes were visualized using the TriPlot approach.

Results:

Out of 17869 omics features, 29 (for OCs) and 12 (for PFAS) metabolite features and proteins associated with exposures and CVD outcomes and selected features were unique to OCs and PFAS exposures. OC-related features associated with increased risk of CVD, whereas the inverse was found for PFAS-related features (for myocardial infarction). Associations of POP-related features with exposures and CVD outcomes were diluted by adjustment for age and BMI for OCs but not for PFAS. Whilst most of the PFAS-related features still need to be annotated, several of the OC-related features indicate involvement of lipids and the aryl hydrocarbon receptor pathway.

Conclusions:

These results imply different molecular pathways with opposite effects on CVD risk for OCs and PFAS.

Presentation format: Flash presentation & Poster