Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach
| Autor: | Anho H Liem, Albert Hofman, Adriana C. Blommesteijn-Touw, Iris Kindt, Jeanette Erdman, Mojgan Yazdanpanah, Fátima Almagro, Frans van der Ouderaa, Ranitha Vongpromek, Fernando Civeira, Jose M. Ordovas, Peter W. de Leeuw, Keith J. Johnson, Hrobjartur D. Karlsson, Monique T. Mulder, Daniëlla M. Oosterveer, Tony Dadd, Martin R. Green, Joep C. Defesche, Roeland Huijgen, Abbas Dehghan, Maarten L. Simoons, Hilma Holm, Leonie C. van Vark-van der Zee, Leiv Ose, Aeilko H. Zwinderman, Cornelia M. van Duijn, Gisle Langslet, Luis Masana, Maurizio Averna, Gudmar Thorleifsson, Jorie Versmissen, A F L Schinkel, Jaap Kwekkeboom, Yurii S. Aulchenko, Jacqueline C. M. Witteman, John J.P. Kastelein, Heribert Schunkert, Steve E. Humphries, Arne S. Schaefer, Stefano Bertolini, Emilio Ros, Xavier Pintó, Andrew Neil, André G. Uitterlinden, Eric J.G. Sijbrands, Amelia Jarman, Sebastiano Calandra |
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| Přispěvatelé: | Other departments, Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine, Amsterdam Public Health, Epidemiology and Data Science, Vascular Medicine, Psychiatrie & Neuropsychologie, MUMC+: MA Alg Interne Geneeskunde (9), RS: CARIM - R3 - Vascular biology, Interne Geneeskunde, Family Medicine, 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, Internal Medicine, Epidemiology, Gastroenterology & Hepatology, Cardiology |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Risk Settore MED/09 - Medicina Interna Genotype Population Coronary Disease Single-nucleotide polymorphism Genome-wide association study Comorbidity Familial hypercholesterolemia Quantitative trait locus Biology medicine.disease_cause Polymorphism Single Nucleotide Article Hyperlipoproteinemia Type II Young Adult symbols.namesake Gene Frequency Risk Factors Odds Ratio Genetics medicine Humans Genetic Predisposition to Disease education Alleles Genetics (clinical) Aged Aged 80 and over Mutation education.field_of_study familial hypercholesterolemia PCSK9 genetic risk factor Genetic Variation Middle Aged medicine.disease Bonferroni correction Receptors LDL Case-Control Studies symbols Female Genome-Wide Association Study |
| Zdroj: | European journal of human genetics, 23(3), 381-387. Nature Publishing Group European Journal of Human Genetics, 23(3), 381-387. Nature Publishing Group European Journal of Human Genetics, 23(3), 381-387 |
| ISSN: | 1018-4813 |
| DOI: | 10.1038/ejhg.2014.101 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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