Börge Schmidt1, Stefanie Frölich2, Nico Dragano2, Mirjam Frank2, Lewin Eisele2, Sonali Pechlivanis2, Andreas J Forstner2, Markus M Nöthen2, Amir A Mahabadi2, Raimund Erbel2, Susanne Moebus2, Karl-Heinz Jöckel2. 1. From the Institute for Medical Informatics, Biometry and Epidemiology (B.S., S.F., M.F., L.E., S.P., R.E., S.M., K.-H.J.), West-German Heart and Vascular Center Essen, Department of Cardiology (A.A.M.), University of Duisburg-Essen, Germany; Institute for Medical Sociology, Centre for Health and Society, Medical Faculty, University Clinic Düsseldorf, Germany (N.D.); Institute of Human Genetics (A.J.F., M.M.N.), Department of Genomics, Life and Brain Center (A.J.F., M.M.N.), University of Bonn, Germany. boerge.schmidt@uk-essen.de. 2. From the Institute for Medical Informatics, Biometry and Epidemiology (B.S., S.F., M.F., L.E., S.P., R.E., S.M., K.-H.J.), West-German Heart and Vascular Center Essen, Department of Cardiology (A.A.M.), University of Duisburg-Essen, Germany; Institute for Medical Sociology, Centre for Health and Society, Medical Faculty, University Clinic Düsseldorf, Germany (N.D.); Institute of Human Genetics (A.J.F., M.M.N.), Department of Genomics, Life and Brain Center (A.J.F., M.M.N.), University of Bonn, Germany.
Abstract
BACKGROUND: Genetic variants of a locus within the chromosome 9p21.3 region are consistently associated with coronary artery disease and coronary artery calcification (CAC). The aim of this study was to examine whether a 9p21.3 common variant interacts with socioeconomic status (SES) to influence CAC and incident coronary events in a population-based cohort. METHODS AND RESULTS: 9p21.3 single nucleotide polymorphism rs2891168 was genotyped in 4116 participants of the Heinz Nixdorf Recall study. SES indicators (education and income) and CAC were assessed at baseline. Incident coronary events were ascertained over a median follow-up of 9.3 years. Multiple regression models were fitted to estimate genetic effects on loge(CAC+1) and incident coronary events. Genetic effects were highest in the lower income tertile with a 53.1% (95% confidence interval, 30.6%-79.6%; P=1.8×10 -7) increase in CAC and a hazard ratio of 1.44 (95% confidence interval, 1.01-2.07; P=0.049) for incident coronary events per additional risk allele. After including genotype×SES interaction terms in the regression models, genotype×income interactions were observed for CAC (exp[βg×income]=0.85 [95% confidence interval, 0.74-0.98; Pg×income=0.02] per 1000€/mo increase and additional risk allele) and for incident coronary events (hazard ratiog×income=0.69 [95% confidence interval, 0.48-0.98; Pg×income=0.04] per 1000€/mo increase and additional risk allele). No interaction was observed using education as SES indicator. CONCLUSIONS: A 9p21.3 common variant seems to interact with SES to influence CAC and incident coronary events in a population-based cohort. This supports the hypothesis that better material, psychosocial, and lifestyle conditions enable higher SES groups to reduce the expression of their genetic susceptibility to coronary artery disease.
BACKGROUND: Genetic variants of a locus within the chromosome 9p21.3 region are consistently associated with coronary artery disease and coronary artery calcification (CAC). The aim of this study was to examine whether a 9p21.3 common variant interacts with socioeconomic status (SES) to influence CAC and incident coronary events in a population-based cohort. METHODS AND RESULTS: 9p21.3 single nucleotide polymorphism rs2891168 was genotyped in 4116 participants of the Heinz Nixdorf Recall study. SES indicators (education and income) and CAC were assessed at baseline. Incident coronary events were ascertained over a median follow-up of 9.3 years. Multiple regression models were fitted to estimate genetic effects on loge(CAC+1) and incident coronary events. Genetic effects were highest in the lower income tertile with a 53.1% (95% confidence interval, 30.6%-79.6%; P=1.8×10 -7) increase in CAC and a hazard ratio of 1.44 (95% confidence interval, 1.01-2.07; P=0.049) for incident coronary events per additional risk allele. After including genotype×SES interaction terms in the regression models, genotype×income interactions were observed for CAC (exp[βg×income]=0.85 [95% confidence interval, 0.74-0.98; Pg×income=0.02] per 1000€/mo increase and additional risk allele) and for incident coronary events (hazard ratiog×income=0.69 [95% confidence interval, 0.48-0.98; Pg×income=0.04] per 1000€/mo increase and additional risk allele). No interaction was observed using education as SES indicator. CONCLUSIONS: A 9p21.3 common variant seems to interact with SES to influence CAC and incident coronary events in a population-based cohort. This supports the hypothesis that better material, psychosocial, and lifestyle conditions enable higher SES groups to reduce the expression of their genetic susceptibility to coronary artery disease.
Authors: Alice R Carter; Sean Harrison; Dipender Gill; George Davey Smith; Amy E Taylor; Laura D Howe; Neil M Davies Journal: Int J Epidemiol Date: 2022-06-13 Impact factor: 9.685