%0 Journal Article
%T Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses
%A Stella Trompet
%A Anton JM de Craen
%A Iris Postmus
%A Ian Ford
%A Naveed Sattar
%A Muriel Caslake
%A David J Stott
%A Brendan M Buckley
%A Frank Sacks
%A James J Devlin
%A P Slagboom
%A Rudi GJ Westendorp
%A J Jukema
%A the PROSPER study group
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-131
%X The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.Cardiovascular disease is the leading cause of death in industrialized countries at old age. Advancing age is one of the most important risk factors for cardiovascular disease [1]. With the rising number of elderly people in our society cardiovascular disease has a major impact on healthcare [2]. The prevention of cardiovascular disease is critically dependent on lipid lowe
%U http://www.biomedcentral.com/1471-2350/12/131