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A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave
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 tri...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106801/ https://www.ncbi.nlm.nih.gov/pubmed/25050552 http://dx.doi.org/10.1371/journal.pone.0102113 |
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author | Lamina, Claudia Haun, Margot Coassin, Stefan Kloss-Brandstätter, Anita Gieger, Christian Peters, Annette Grallert, Harald Strauch, Konstantin Meitinger, Thomas Kedenko, Lyudmyla Paulweber, Bernhard Kronenberg, Florian |
author_facet | Lamina, Claudia Haun, Margot Coassin, Stefan Kloss-Brandstätter, Anita Gieger, Christian Peters, Annette Grallert, Harald Strauch, Konstantin Meitinger, Thomas Kedenko, Lyudmyla Paulweber, Bernhard Kronenberg, Florian |
author_sort | Lamina, Claudia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4106801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41068012014-07-23 A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave Lamina, Claudia Haun, Margot Coassin, Stefan Kloss-Brandstätter, Anita Gieger, Christian Peters, Annette Grallert, Harald Strauch, Konstantin Meitinger, Thomas Kedenko, Lyudmyla Paulweber, Bernhard Kronenberg, Florian PLoS One Research Article 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. Public Library of Science 2014-07-22 /pmc/articles/PMC4106801/ /pubmed/25050552 http://dx.doi.org/10.1371/journal.pone.0102113 Text en © 2014 Lamina et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lamina, Claudia Haun, Margot Coassin, Stefan Kloss-Brandstätter, Anita Gieger, Christian Peters, Annette Grallert, Harald Strauch, Konstantin Meitinger, Thomas Kedenko, Lyudmyla Paulweber, Bernhard Kronenberg, Florian A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave |
title | A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave |
title_full | A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave |
title_fullStr | A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave |
title_full_unstemmed | A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave |
title_short | A Systematic Evaluation of Short Tandem Repeats in Lipid Candidate Genes: Riding on the SNP-Wave |
title_sort | systematic evaluation of short tandem repeats in lipid candidate genes: riding on the snp-wave |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106801/ https://www.ncbi.nlm.nih.gov/pubmed/25050552 http://dx.doi.org/10.1371/journal.pone.0102113 |
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