title: A systematic evaluation of short tandem repeats in lipid candidate genes: riding on the SNP-wave.
abstract: Structural genetic variants as short tandem repeats (STRs) are not targeted in SNP-based association studies and thus, their possible association signals are missed. We systematically searched for STRs in gene regions known to contribute to total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels in two independent studies (KORA F4, n = 2553 and SAPHIR, n = 1648), resulting in 16 STRs that were finally evaluated. In a combined dataset of both studies, the sum of STR alleles was regressed on each phenotype, adjusted for age and sex. The association analyses were repeated for SNPs in a 200 kb region surrounding the respective STRs in the KORA F4 Study. Three STRs were significantly associated with total cholesterol (within LDLR, the APOA1/C3/A4/A5/BUD13 gene region and ABCG5/8), five with HDL cholesterol (3 within CETP, one in LPL and one inAPOA1/C3/A4/A5/BUD13), three with LDL cholesterol (LDLR, ABCG5/8 and CETP) and two with triglycerides (APOA1/C3/A4/A5/BUD13 and LPL). None of the investigated STRs, however, showed a significant association after adjusting for the lead or adjacent SNPs within that gene region. The evaluated STRs were found to be well tagged by the lead SNP within the respective gene regions. Therefore, the STRs reflect the association signals based on surrounding SNPs. In conclusion, none of the STRs contributed additionally to the SNP-based association signals identified in GWAS on lipid traits.
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Claudia
authors: C
authors: Lamina
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Margot
authors: M
authors: Haun
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Stefan
authors: S
authors: Coassin
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Anita
authors: A
authors: Kloss-Brandstätter
authors: Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
authors: Christian
authors: C
authors: Gieger
authors: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Annette
authors: A
authors: Peters
authors: Department of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Harald
authors: H
authors: Grallert
authors: Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Konstantin
authors: K
authors: Strauch
authors: Institute of Human Genetics, TechnischeUniversitätMünchen, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Thomas
authors: T
authors: Meitinger
authors: First Department of Internal Medicine, Paracelsus Private Medical University Salzburg, Salzburg, Austria.
authors: Lyudmyla
authors: L
authors: Kedenko
authors: First Department of Internal Medicine, Paracelsus Private Medical University Salzburg, Salzburg, Austria.
authors: Bernhard
authors: B
authors: Paulweber
authors: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors: Florian
authors: F
authors: Kronenberg
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D056726:Genetic Association Studies; D006801:Humans; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D011973:Receptors, LDL