OBJECTIVE: SNP/phenotype associations are difficult to validate. This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach. METHODS: Independent samples of normolipidemic subjects from two Caucasian populations (371 Swiss and 157 Germans) were selected for a case-control-study (high LDL/low HDL versus low LDL/high HDL) with SNP genotypes as independent factors. We examined locus-specific common SNPs that densely cover the genomic regions of 10 lipid genes. RESULTS: Genotype effects were concordant in both ethnic samples, showing that APOE, ABCA1, CETP, and to a lesser degree LDLR, LIPC, and PLTP explained a substantial part of the genetic variation, whereas LPL was associated in only one sample. APOA1, LCAT, and SRB1 exerted no measurable influence. CONCLUSION: This comparison showed that sets of common SNPs representing candidate regions reproducibly validate significant linkage disequilibrium association with a complex metabolic trait. Copyright (c) 2006 S. Karger AG, Basel.
OBJECTIVE: SNP/phenotype associations are difficult to validate. This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach. METHODS: Independent samples of normolipidemic subjects from two Caucasian populations (371 Swiss and 157 Germans) were selected for a case-control-study (high LDL/low HDL versus low LDL/high HDL) with SNP genotypes as independent factors. We examined locus-specific common SNPs that densely cover the genomic regions of 10 lipid genes. RESULTS: Genotype effects were concordant in both ethnic samples, showing that APOE, ABCA1, CETP, and to a lesser degree LDLR, LIPC, and PLTP explained a substantial part of the genetic variation, whereas LPL was associated in only one sample. APOA1, LCAT, and SRB1 exerted no measurable influence. CONCLUSION: This comparison showed that sets of common SNPs representing candidate regions reproducibly validate significant linkage disequilibrium association with a complex metabolic trait. Copyright (c) 2006 S. Karger AG, Basel.
Authors: Patrick Linsel-Nitschke; Anika Götz; Jeanette Erdmann; Ingrid Braenne; Peter Braund; Christian Hengstenberg; Klaus Stark; Marcus Fischer; Stefan Schreiber; Nour Eddine El Mokhtari; Arne Schaefer; Jürgen Schrezenmeir; Jürgen Schrezenmeier; Diana Rubin; Anke Hinney; Thomas Reinehr; Christian Roth; Jan Ortlepp; Peter Hanrath; Alistair S Hall; Massimo Mangino; Wolfgang Lieb; Claudia Lamina; Iris M Heid; Angela Doering; Christian Gieger; Annette Peters; Thomas Meitinger; H-Erich Wichmann; Inke R König; Andreas Ziegler; Florian Kronenberg; Nilesh J Samani; Heribert Schunkert Journal: PLoS One Date: 2008-08-20 Impact factor: 3.240