 | Palwende Romuald Boua, Jean-Tristan Brandenburg, Ananyo Choudhury, Scott Hazelhurst, Dhriti Sengupta, Godfred Agongo, Engelbert A Nonterah, Abraham R Oduro, Halidou Tinto, Christopher G Mathew, Hermann Sorgho, Mich`ele Ramsay Novel and known gene-smoking interactions with cIMT identified as potential drivers for atherosclerosis risk in West-African populations of the AWI-gen study (Journal Article) In: Front. Genet., vol. 10, pp. 1354, 2019. @article{Boua2019-um,
title = {Novel and known gene-smoking interactions with cIMT identified as potential drivers for atherosclerosis risk in West-African populations of the AWI-gen study},
author = {Palwende Romuald Boua and Jean-Tristan Brandenburg and Ananyo Choudhury and Scott Hazelhurst and Dhriti Sengupta and Godfred Agongo and Engelbert A Nonterah and Abraham R Oduro and Halidou Tinto and Christopher G Mathew and Hermann Sorgho and Mich`ele Ramsay},
doi = {10.3389/fgene.2019.01354},
year = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {Front. Genet.},
volume = {10},
pages = {1354},
publisher = {Frontiers Media SA},
abstract = {Introduction: Atherosclerosis 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 methods: Only 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. Results:
In 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).
Discussion: This 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.},
keywords = {GWIS; atherosclerosis; carotid intima-media thickness; gene-environment interactions; smoking},
pubstate = {published},
tppubtype = {article}
}
Introduction: Atherosclerosis 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 methods: Only 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. Results:
In 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).
Discussion: This 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. |
