Cross-sectional gene-smoking interaction analysis in relation to subclinical atherosclerosis-results from the IMPROVE study

Maitusong, B. et al. (2023) Cross-sectional gene-smoking interaction analysis in relation to subclinical atherosclerosis-results from the IMPROVE study. Circulation: Genomic and Precision Medicine, 16(3), pp. 236-247. (doi: 10.1161/CIRCGEN.122.003710) (PMID:37021583) (PMCID:PMC10284137)

Abstract

Background: Smoking is associated with carotid intima-media thickness (C-IMT). However, knowledge about how genetics may influence this association is limited. We aimed to perform nonhypothesis driven gene-smoking interaction analyses to identify potential genetic variants, among those included in immune and metabolic platforms, that may modify the effect of smoking on carotid intima-media thickness. Materials: We used baseline data from 1551 men and 1700 women, aged 55 to 79, included in a European multi-center study. Carotid intima-media thickness maximum, the maximum of values measured at different locations of the carotid tree, was dichotomized with cut point values ≥75, respectively. Genetic data were retrieved through use of the Illumina Cardio-Metabo- and Immuno- Chips. Gene-smoking interactions were evaluated through calculations of Synergy index (S). After adjustments for multiple testing, P values of <2.4×10−7 for S were considered significant. The models were adjusted for age, sex, education, physical activity, type of diet, and population stratification. Results: Our screening of 207 586 SNPs available for analysis, resulted in the identification of 47 significant gene-smoking synergistic interactions in relation to carotid intima-media thickness maximum. Among the significant SNPs, 28 were in protein coding genes, 2 in noncoding RNA and the remaining 17 in intergenic regions. Conclusions: Through nonhypothesis-driven analyses of gene-smoking interactions, several significant results were observed. These may stimulate further research on the role of specific genes in the process that determines the effect of smoking habits on the development of carotid atherosclerosis.

• Item Type: Articles
• Additional Information: The IMPROVE study (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) was supported by the European Commission (contract number: QLG1- CT- 2002- 00896; to Drs Tremoli, Baldassarre, Giral, Kurl, Pirro); Ministero della Salute Ricerca Corrente, Italy (RC2017 BIO30 ID:2631169; RC2018 MMP4.9 ID:2634520; RC2019 MPP 4D ID:2755475; to Dr Baldassarre). The IMPROVE was also funded by the Swedish Research Council (8691 and 0593), European Commission (contract number: QLG1- CT- 2002- 00896), the Swedish Heart-Lung Foundation, the Swedish Foundation for Strategic Research, the Stockholm County Council (project 562183), and the British Heart Foundation (RG2008/008). The present study was supported by the Swedish Research Council (project 2016-02815 to Dr Leander). Dr Strawbridge is supported by a UKRI Innovation-HDR-UK Fellowship (MR/S003061/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Strawbridge, Dr Rona
• Authors: Maitusong, B., Laguzzi, F., Strawbridge, R. J., Baldassarre, D., Veglia, F., Humphries, S. E., Savonen, K., Kurl, S., Pirro, M., Smit, A. J., Giral, P., Silveira, A., Tremoli, E., Hamsten, A., de Faire, U., Gigante, B., and Leander, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Circulation: Genomic and Precision Medicine
• Publisher: American Heart Association
• ISSN: 2574-8300
• ISSN (Online): 2574-8300
• Published Online: 06 April 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Circulation: Genomic and Precision Medicine 16(3):236-247
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302131		Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness	Jill Pell	Medical Research Council (MRC)	MR/S003061/1	HW - Public Health