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Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos

BACKGROUND: Despite ethnic disparities in lipid profiles, there are few genome-wide association studies investigating genetic variation of lipids in non-European ancestry populations. In this study, we present findings from genetic association analyses for total cholesterol, low density lipoprotein...

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Autores principales: Graff, Mariaelisa, Emery, Leslie S., Justice, Anne E., Parra, Esteban, Below, Jennifer E., Palmer, Nicholette D., Gao, Chuan, Duan, Qing, Valladares-Salgado, Adan, Cruz, Miguel, Morrison, Alanna C., Boerwinkle, Eric, Whitsel, Eric A., Kooperberg, Charles, Reiner, Alex, Li, Yun, Rodriguez, Carlos Jose, Talavera, Gregory A., Langefeld, Carl D., Wagenknecht, Lynne E., Norris, Jill M., Taylor, Kent D., Papanicolaou, George, Kenny, Eimear, Loos, Ruth J. F., Chen, Yii-Der Ida, Laurie, Cathy, Sofer, Tamar, North, Kari E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639746/
https://www.ncbi.nlm.nih.gov/pubmed/29025430
http://dx.doi.org/10.1186/s12944-017-0591-6
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author Graff, Mariaelisa
Emery, Leslie S.
Justice, Anne E.
Parra, Esteban
Below, Jennifer E.
Palmer, Nicholette D.
Gao, Chuan
Duan, Qing
Valladares-Salgado, Adan
Cruz, Miguel
Morrison, Alanna C.
Boerwinkle, Eric
Whitsel, Eric A.
Kooperberg, Charles
Reiner, Alex
Li, Yun
Rodriguez, Carlos Jose
Talavera, Gregory A.
Langefeld, Carl D.
Wagenknecht, Lynne E.
Norris, Jill M.
Taylor, Kent D.
Papanicolaou, George
Kenny, Eimear
Loos, Ruth J. F.
Chen, Yii-Der Ida
Laurie, Cathy
Sofer, Tamar
North, Kari E.
author_facet Graff, Mariaelisa
Emery, Leslie S.
Justice, Anne E.
Parra, Esteban
Below, Jennifer E.
Palmer, Nicholette D.
Gao, Chuan
Duan, Qing
Valladares-Salgado, Adan
Cruz, Miguel
Morrison, Alanna C.
Boerwinkle, Eric
Whitsel, Eric A.
Kooperberg, Charles
Reiner, Alex
Li, Yun
Rodriguez, Carlos Jose
Talavera, Gregory A.
Langefeld, Carl D.
Wagenknecht, Lynne E.
Norris, Jill M.
Taylor, Kent D.
Papanicolaou, George
Kenny, Eimear
Loos, Ruth J. F.
Chen, Yii-Der Ida
Laurie, Cathy
Sofer, Tamar
North, Kari E.
author_sort Graff, Mariaelisa
collection PubMed
description BACKGROUND: Despite ethnic disparities in lipid profiles, there are few genome-wide association studies investigating genetic variation of lipids in non-European ancestry populations. In this study, we present findings from genetic association analyses for total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides in a large Hispanic/Latino cohort in the U.S., the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). METHODS: We estimated a heritability of approximately 20% for each lipid trait, similar to previous estimates in Europeans. To search for novel lipid loci, we performed conditional association analysis in which the statistical model was adjusted for previously reported SNPs associated with any of the four lipid traits. SNPs that remained genome-wide significant (P < 5 × 10(−8)) after conditioning on known loci were evaluated for replication. RESULTS: We identified eight potentially novel lipid signals with minor allele frequencies <1%, none of which replicated. We tested previously reported SNP-trait associations for generalization to Hispanics/Latinos via a statistical framework. The generalization analysis revealed that approximately 50% of previously established lipid variants generalize to HCHS/SOL based on directional FDR r-value < 0.05. Some failures to generalize were due to lack of power. CONCLUSIONS: These results demonstrate that many loci associated with lipid levels are shared across populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-017-0591-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-56397462017-10-18 Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos Graff, Mariaelisa Emery, Leslie S. Justice, Anne E. Parra, Esteban Below, Jennifer E. Palmer, Nicholette D. Gao, Chuan Duan, Qing Valladares-Salgado, Adan Cruz, Miguel Morrison, Alanna C. Boerwinkle, Eric Whitsel, Eric A. Kooperberg, Charles Reiner, Alex Li, Yun Rodriguez, Carlos Jose Talavera, Gregory A. Langefeld, Carl D. Wagenknecht, Lynne E. Norris, Jill M. Taylor, Kent D. Papanicolaou, George Kenny, Eimear Loos, Ruth J. F. Chen, Yii-Der Ida Laurie, Cathy Sofer, Tamar North, Kari E. Lipids Health Dis Research BACKGROUND: Despite ethnic disparities in lipid profiles, there are few genome-wide association studies investigating genetic variation of lipids in non-European ancestry populations. In this study, we present findings from genetic association analyses for total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides in a large Hispanic/Latino cohort in the U.S., the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). METHODS: We estimated a heritability of approximately 20% for each lipid trait, similar to previous estimates in Europeans. To search for novel lipid loci, we performed conditional association analysis in which the statistical model was adjusted for previously reported SNPs associated with any of the four lipid traits. SNPs that remained genome-wide significant (P < 5 × 10(−8)) after conditioning on known loci were evaluated for replication. RESULTS: We identified eight potentially novel lipid signals with minor allele frequencies <1%, none of which replicated. We tested previously reported SNP-trait associations for generalization to Hispanics/Latinos via a statistical framework. The generalization analysis revealed that approximately 50% of previously established lipid variants generalize to HCHS/SOL based on directional FDR r-value < 0.05. Some failures to generalize were due to lack of power. CONCLUSIONS: These results demonstrate that many loci associated with lipid levels are shared across populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-017-0591-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-12 /pmc/articles/PMC5639746/ /pubmed/29025430 http://dx.doi.org/10.1186/s12944-017-0591-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Graff, Mariaelisa
Emery, Leslie S.
Justice, Anne E.
Parra, Esteban
Below, Jennifer E.
Palmer, Nicholette D.
Gao, Chuan
Duan, Qing
Valladares-Salgado, Adan
Cruz, Miguel
Morrison, Alanna C.
Boerwinkle, Eric
Whitsel, Eric A.
Kooperberg, Charles
Reiner, Alex
Li, Yun
Rodriguez, Carlos Jose
Talavera, Gregory A.
Langefeld, Carl D.
Wagenknecht, Lynne E.
Norris, Jill M.
Taylor, Kent D.
Papanicolaou, George
Kenny, Eimear
Loos, Ruth J. F.
Chen, Yii-Der Ida
Laurie, Cathy
Sofer, Tamar
North, Kari E.
Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos
title Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos
title_full Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos
title_fullStr Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos
title_full_unstemmed Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos
title_short Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos
title_sort genetic architecture of lipid traits in the hispanic community health study/study of latinos
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639746/
https://www.ncbi.nlm.nih.gov/pubmed/29025430
http://dx.doi.org/10.1186/s12944-017-0591-6
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