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Serum lipid levels, body mass index, and their role in coronary artery calcification: a polygenic analysis.
van Setten, Jessica; Isgum, Ivana; Pechlivanis, Sonali; Tragante, Vinicius; de Jong, Pim A; Smolonska, Joanna; Platteel, Mathieu; Hoffmann, Per; Oudkerk, Matthijs; de Koning, Harry J; Nöthen, Markus M; Moebus, Susanne; Erbel, Raimund; Jöckel, Karl-Heinz; Viergever, Max A; Mali, Willem P Th M; de Bakker, Paul I W.
  • van Setten J; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Isgum I; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Pechlivanis S; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Tragante V; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • de Jong PA; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Smolonska J; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Platteel M; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Hoffmann P; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Oudkerk M; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • de Koning HJ; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Nöthen MM; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Moebus S; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Erbel R; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Jöckel KH; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Viergever MA; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • Mali WP; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
  • de Bakker PI; From the Department of Medical Genetics, Center for Molecular Medicine (J.v.S., P.I.W.d.B.), Image Sciences Institute (I.I., M.A.V.), Department of Cardiology (V.T.); Department of Radiology (P.A.d.J.), Department of Epidemiology, Julius Center for Health Sciences and Primary Care (P.I.W.d.B.), Univ
Circ Cardiovasc Genet ; 8(2): 327-33, 2015 Apr.
Article en En | MEDLINE | ID: mdl-25577604
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Índice de Masa Corporal / Herencia Multifactorial / Calcificación Vascular / Lípidos Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País como asunto: Europa Idioma: En Año: 2015 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Índice de Masa Corporal / Herencia Multifactorial / Calcificación Vascular / Lípidos Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País como asunto: Europa Idioma: En Año: 2015 Tipo del documento: Article