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Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits

BACKGROUND: Genome-wide association studies (GWAS) have become a major strategy for genetic dissection of human complex diseases. Analysing multiple phenotypes jointly may improve both our ability to detect genetic variants with multiple effects and our understanding of their common features. Alleli...

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Autores principales: Middelberg, Rita PS, Ferreira, Manuel AR, Henders, Anjali K, Heath, Andrew C, Madden, Pamela AF, Montgomery, Grant W, Martin, Nicholas G, Whitfield, John B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189113/
https://www.ncbi.nlm.nih.gov/pubmed/21943158
http://dx.doi.org/10.1186/1471-2350-12-123
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author Middelberg, Rita PS
Ferreira, Manuel AR
Henders, Anjali K
Heath, Andrew C
Madden, Pamela AF
Montgomery, Grant W
Martin, Nicholas G
Whitfield, John B
author_facet Middelberg, Rita PS
Ferreira, Manuel AR
Henders, Anjali K
Heath, Andrew C
Madden, Pamela AF
Montgomery, Grant W
Martin, Nicholas G
Whitfield, John B
author_sort Middelberg, Rita PS
collection PubMed
description BACKGROUND: Genome-wide association studies (GWAS) have become a major strategy for genetic dissection of human complex diseases. Analysing multiple phenotypes jointly may improve both our ability to detect genetic variants with multiple effects and our understanding of their common features. Allelic associations for multiple biochemical traits (serum alanine aminotransferase, aspartate aminotransferase, butrylycholinesterase (BCHE), C-reactive protein (CRP), ferritin, gamma glutamyltransferase (GGT), glucose, high-density lipoprotein cholesterol (HDL), insulin, low-density lipoprotein cholesterol (LDL), triglycerides and uric acid), and body-mass index, were examined. METHODS: We aimed to identify common genetic variants affecting more than one of these traits using genome-wide association analysis in 2548 adolescents and 9145 adults from 4986 Australian twin families. Multivariate and univariate associations were performed. RESULTS: Multivariate analyses identified eight loci, and univariate association analyses confirmed two loci influencing more than one trait at p < 5 × 10(-8). These are located on chromosome 8 (LPL gene affecting HDL and triglycerides) and chromosome 19 (TOMM40/APOE-C1-C2-C4 gene cluster affecting LDL and CRP). A locus on chromosome 12 (OASL gene) showed effects on GGT, LDL and CRP. The loci on chromosomes 12 and 19 unexpectedly affected LDL cholesterol and CRP in opposite directions. CONCLUSIONS: We identified three possible loci that may affect multiple traits and validated 17 previously-reported loci. Our study demonstrated the usefulness of examining multiple phenotypes jointly and highlights an anomalous effect on CRP, which is increasingly recognised as a marker of cardiovascular risk as well as of inflammation.
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spelling pubmed-31891132011-10-08 Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits Middelberg, Rita PS Ferreira, Manuel AR Henders, Anjali K Heath, Andrew C Madden, Pamela AF Montgomery, Grant W Martin, Nicholas G Whitfield, John B BMC Med Genet Research Article BACKGROUND: Genome-wide association studies (GWAS) have become a major strategy for genetic dissection of human complex diseases. Analysing multiple phenotypes jointly may improve both our ability to detect genetic variants with multiple effects and our understanding of their common features. Allelic associations for multiple biochemical traits (serum alanine aminotransferase, aspartate aminotransferase, butrylycholinesterase (BCHE), C-reactive protein (CRP), ferritin, gamma glutamyltransferase (GGT), glucose, high-density lipoprotein cholesterol (HDL), insulin, low-density lipoprotein cholesterol (LDL), triglycerides and uric acid), and body-mass index, were examined. METHODS: We aimed to identify common genetic variants affecting more than one of these traits using genome-wide association analysis in 2548 adolescents and 9145 adults from 4986 Australian twin families. Multivariate and univariate associations were performed. RESULTS: Multivariate analyses identified eight loci, and univariate association analyses confirmed two loci influencing more than one trait at p < 5 × 10(-8). These are located on chromosome 8 (LPL gene affecting HDL and triglycerides) and chromosome 19 (TOMM40/APOE-C1-C2-C4 gene cluster affecting LDL and CRP). A locus on chromosome 12 (OASL gene) showed effects on GGT, LDL and CRP. The loci on chromosomes 12 and 19 unexpectedly affected LDL cholesterol and CRP in opposite directions. CONCLUSIONS: We identified three possible loci that may affect multiple traits and validated 17 previously-reported loci. Our study demonstrated the usefulness of examining multiple phenotypes jointly and highlights an anomalous effect on CRP, which is increasingly recognised as a marker of cardiovascular risk as well as of inflammation. BioMed Central 2011-09-24 /pmc/articles/PMC3189113/ /pubmed/21943158 http://dx.doi.org/10.1186/1471-2350-12-123 Text en Copyright ©2011 Middelberg et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Middelberg, Rita PS
Ferreira, Manuel AR
Henders, Anjali K
Heath, Andrew C
Madden, Pamela AF
Montgomery, Grant W
Martin, Nicholas G
Whitfield, John B
Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits
title Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits
title_full Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits
title_fullStr Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits
title_full_unstemmed Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits
title_short Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits
title_sort genetic variants in lpl, oasl and tomm40/apoe-c1-c2-c4 genes are associated with multiple cardiovascular-related traits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189113/
https://www.ncbi.nlm.nih.gov/pubmed/21943158
http://dx.doi.org/10.1186/1471-2350-12-123
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