Serum lipid levels, body mass index, and their role in coronary artery calcification : a polygenic analysis
| Autor: | Willem P.Th.M. Mali, Susanne Moebus, Mathieu Platteel, Per Hoffmann, Max A. Viergever, Jessica van Setten, Markus M. Nöthen, Harry J. de Koning, Vinicius Tragante, Joanna Smolonska, Paul I.W. de Bakker, Karl-Heinz Jöckel, Sonali Pechlivanis, Matthijs Oudkerk, Raimund Erbel, Pim A. de Jong, Ivana Išgum |
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| Přispěvatelé: | Public Health, Academic Medical Center |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
CALCIUM SCORE Pathology medicine.medical_specialty Multifactorial Inheritance PROVIDES INSIGHTS Medizin Genome-wide association study BLOOD-PRESSURE Body Mass Index GENETIC ARCHITECTURE Coronary artery disease Belgium SDG 3 - Good Health and Well-being Internal medicine Genetics medicine Humans COMPUTED-TOMOGRAPHY Myocardial infarction cardiovascular diseases GENOME-WIDE ASSOCIATION Vascular Calcification ASYMPTOMATIC INDIVIDUALS Genetics (clinical) Netherlands genome-wide association study RISK PREDICTION business.industry nutritional and metabolic diseases medicine.disease Lipids Arterial calcification Blood pressure myocardial infarction MYOCARDIAL-INFARCTION CARDIOVASCULAR-DISEASE Cardiology Female Cardiology and Cardiovascular Medicine business Body mass index Lung cancer screening coronary artery disease Calcification |
| Zdroj: | Circulation-cardiovascular genetics, 8(2), 327-333. Lippincott Williams & Wilkins Circulation-Cardiovascular genetics, 8(2), 327. Lippincott Williams and Wilkins Circulation-Cardiovascular Genetics, 8(2), 327-333. LIPPINCOTT WILLIAMS & WILKINS Circulation. Cardiovascular genetics, 8(2), 327-333. Lippincott Williams and Wilkins |
| ISSN: | 1942-325X |
| Popis: | Background— Coronary artery calcification (CAC) is widely regarded as a cumulative lifetime measure of atherosclerosis, but it remains unclear what is the relationship between calcification and traditional risk factors for coronary artery disease (CAD) and myocardial infarction (MI). This study characterizes the genetic architecture of CAC by evaluating the overall impact of common alleles associated with CAD/MI and its traditional risk factors. Methods and Results— On the basis of summary-association results from the CARDIoGRAMplusC4D study of CAD/MI, we calculated polygenic risk scores in 2599 participants of the Dutch and Belgian Lung Cancer Screening (NELSON) trial, in whom quantitative CAC levels (Agatston scores) were determined from chest computerized tomographic imaging data. The most significant polygenic model explained ≈14% of the observed CAC variance ( P =1.6×10 –11 ), which points to a residual effect because of many as yet unknown loci that overlap between CAD/MI and CAC. In addition, we constructed risk scores based on published single-nucleotide polymorphism associations for traditional cardiovascular risk factors and tested these scores for association with CAC. We found nominally significant associations for genetic risk scores of low-density lipoprotein-cholesterol, total cholesterol, and body mass index, which were successfully replicated in 2182 individuals of the Heinz Nixdorf Recall Study. Conclusions— Pervasive polygenic sharing between CAC and CAD/MI suggests that a substantial fraction of the heritable risk for CAD/MI is mediated through arterial calcification. We also provide evidence that genetic variants associated with serum lipid levels and body mass index influence CAC levels. |
| Databáze: | OpenAIRE |
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