TY - JOUR
T1 - Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach
AU - Versmissen, Jorie
AU - Oosterveer, Daniella M.
AU - Yazdanpanah, Mojgan
AU - Dehghan, Abbas
AU - Holm, Hilma
AU - Erdman, Jeanette
AU - Aulchenko, Yurii S.
AU - Thorleifsson, Gudmar
AU - Schunkert, Heribert
AU - Huijgen, Roeland
AU - Vongpromek, Ranitha
AU - Uitterlinden, Andre G.
AU - Defesche, Joep C.
AU - van Duijn, Cornelia M.
AU - Mulder, Monique
AU - Dadd, Tony
AU - Karlsson, Hrobjartur D.
AU - Ordovas, Jose
AU - Kindt, Iris
AU - Jarman, Amelia
AU - Hofman, Albert
AU - van Vark-van der Zee, Leonie
AU - Blommesteijn-Touw, Adriana C.
AU - Kwekkeboom, Jaap
AU - Liem, Anho H.
AU - van der Ouderaa, Frans J.
AU - Calandra, Sebastiano
AU - Bertolini, Stefano
AU - Averna, Maurizio
AU - Langslet, Gisle
AU - Ose, Leiv
AU - Ros, Emilio
AU - Almagro, Fatima
AU - de Leeuw, Peter W.
AU - Civeira, Fernando
AU - Masana, Luis
AU - Pinto, Xavier
AU - Simoons, Maarten L.
AU - Schinkel, Arend F. L.
AU - Green, Martin R.
AU - Zwinderman, Aeilko H.
AU - Johnson, Keith J.
AU - Schaefer, Arne
AU - Neil, Andrew
AU - Witteman, Jacqueline C. M.
AU - Humphries, Steve E.
AU - Kastelein, John J. P.
AU - Sijbrands, Eric J. G.
PY - 2015/3
Y1 - 2015/3
N2 - 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
AB - 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
U2 - 10.1038/ejhg.2014.101
DO - 10.1038/ejhg.2014.101
M3 - Article
C2 - 24916650
SN - 1018-4813
VL - 23
SP - 381
EP - 387
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 3
ER -