Novel and Known Gene-Smoking Interactions With cIMT Identified as Potential Drivers for Atherosclerosis Risk in West-African Populations of the AWI-Gen Study

Frontiers in Genetics

Halidou Tinto¹  Hermann Sorgho¹  Christopher G. Mathew²  Palwende Romuald Boua³  Michèle Ramsay³  Dhriti Sengupta⁴  Jean-Tristan Brandenburg⁴  Ananyo Choudhury⁴  Engelbert A. Nonterah⁵  Godfred Agongo⁶  Abraham R. Oduro⁶  Scott Hazelhurst⁷ 

[1] Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé, Nanoro, Burkina Faso;Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom;Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;Faculty of Health Sciences, Sydney Brenner Institute for Molecular Bioscience (SBIMB), University of the Witwatersrand, Johannesburg, South Africa;Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands;Navrongo Health Research Centre, Ghana Health Service, Navrongo, Ghana;School of Electrical and Information Engineering, University of the Witwatersrand, Johannesburg, South Africa;

关键词: GWIS;    atherosclerosis;    smoking;    carotid intima-media thickness;    gene-environment interactions;   

DOI  :  10.3389/fgene.2019.01354

来源: DOAJ

【 摘 要 】

IntroductionAtherosclerosis is a key contributor to the burden of cardiovascular diseases (CVDs) and many epidemiological studies have reported on the effect of smoking on carotid intima-media thickness (cIMT) and its subsequent effect on CVD risk. Gene-environment interaction studies have contributed towards understanding some of the missing heritability of genome-wide association studies. Gene-smoking interactions on cIMT have been studied in non-African populations (European, Latino-American, and African American) but no comparable African research has been reported. Our aim was to investigate smoking-SNP interactions on cIMT in two West African populations by genome-wide analysis.Materials and methodsOnly male participants from Burkina Faso (Nanoro = 993) and Ghana (Navrongo = 783) were included, as smoking was extremely rare among women. Phenotype and genotype data underwent stringent QC and genotype imputation was performed using the Sanger African Imputation Panel. Smoking prevalence among men was 13.3% in Nanoro and 42.5% in Navrongo. We analyzed gene-smoking interactions with PLINK after adjusting for covariates: age and 6 PCs (Model 1); age, BMI, blood pressure, fasting glucose, cholesterol levels, MVPA, and 6 PCs (Model 2). All analyses were performed at site level and for the combined data set.ResultsIn Nanoro, we identified new gene-smoking interaction variants for cIMT within the previously described RCBTB1 region (rs112017404, rs144170770, and rs4941649) (Model 1: p = 1.35E-07; Model 2: p = 3.08E-08). In the combined sample, two novel intergenic interacting variants were identified, rs1192824 in the regulatory region of TBC1D8 (p = 5.90E-09) and rs77461169 (p = 4.48E-06) located in an upstream region of open chromatin. In silico functional analysis suggests the involvement of genes implicated in biological processes related to cell or biological adhesion and regulatory processes in gene-smoking interactions with cIMT (as evidenced by chromatin interactions and eQTLs).DiscussionThis is the first gene-smoking interaction study for cIMT, as a risk factor for atherosclerosis, in sub-Saharan African populations. In addition to replicating previously known signals for RCBTB1, we identified two novel genomic regions (TBC1D8, near BCHE) involved in this gene-environment interaction.

【 授权许可】

Unknown