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Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

Title: Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach
Authors: Versmissen, J; Oosterveer, DM; Yazdanpanah, M; Dehghan, A; Hólm, H; Erdman, J; Aulchenko, YS; Thorleifsson, G; Schunkert, H; Huijgen, R; Vongpromek, R; Uitterlinden, AG; Defesche, JC; van Duijn, CM; Mulder, M; Dadd, T; Karlsson, HD; Ordovas, J; Kindt, I; Jarman, A; Hofman, A; van Vark van der Zee, L; Blommesteijn Touw, AC; Kwekkeboom, J; Liem, AH; van der Ouderaa, FJ; Calandra, S; Bertolini, S; AVERNA, Maurizio; Langslet, G; Ose, L; Ros, E; Almagro, F; de Leeuw, PW; Civeira, F; Masana, L; Pintó, X; Simoons, ML; Schinkel, AFL; Green, MR; Zwinderman, AH; Johnson, KJ; Schaefer, A; Neil, A; Witteman, JCM; Humphries, SE; Kastelein, JJP; Sijbrands, EJG
Contributors: Versmissen, J; Oosterveer, DM; Yazdanpanah, M; Dehghan, A; Hólm, H; Erdman, J; Aulchenko, YS; Thorleifsson, G; Schunkert, H; Huijgen, R; Vongpromek, R; Uitterlinden, AG; Defesche, JC; van Duijn, CM; Mulder, M; Dadd, T; Karlsson, HD; Ordovas, J; Kindt, I; Jarman, A; Hofman, A; van Vark-van der Zee, L; Blommesteijn-Touw, AC; Kwekkeboom, J; Liem, AH; van der Ouderaa, FJ; Calandra, S; Bertolini, S; Averna, M; Langslet, G; Ose, L; Ros, E; Almagro, F; de Leeuw, PW; Civeira, F; Masana, L; Pintó, X; Simoons, ML; Schinkel, AFL; Green, MR; Zwinderman, AH; Johnson, KJ; Schaefer, A; Neil, A; Witteman, JCM; Humphries, SE; Kastelein, JJP; Sijbrands, EJG
Publisher Information: GB
Publication Year: 2015
Collection: IRIS Università degli Studi di Palermo
Subject Terms: familial hypercholesterolemia; genetic risk factor; Settore MED/09 - Medicina Interna
Description: Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/wos/WOS:000349670900017; volume:23; issue:3; firstpage:381; lastpage:387; numberofpages:7; journal:EUROPEAN JOURNAL OF HUMAN GENETICS; http://hdl.handle.net/10447/99075
DOI: 10.1038/ejhg.2014.101
Availability: http://hdl.handle.net/10447/99075; https://doi.org/10.1038/ejhg.2014.101
Rights: info:eu-repo/semantics/closedAccess
Accession Number: edsbas.CE9E3A8B
Database: BASE