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

Mariaelisa Graff, Leslie S. Emery, Anne E. Justice, Esteban Parra, Jennifer E. Below, Nicholette D. Palmer, Chuan Gao, Qing Duan, Adan Valladares-Salgado, Miguel Cruz, Alanna C. Morrison, Eric Boerwinkle, Eric A. Whitsel, Charles Kooperberg, Alex Reiner, Yun Li, Carlos Jose Rodriguez, Gregory A. Talavera, Carl D. Langefeld, Lynne E. WagenknechtJill M. Norris, Kent D. Taylor, George Papanicolaou, Eimear Kenny, Ruth J.F. Loos, Yii Der Ida Chen, Cathy Laurie, Tamar Sofer, Kari E. North

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number200
JournalLipids in Health and Disease
Volume16
Issue number1
DOIs
StatePublished - Oct 12 2017
Externally publishedYes

Fingerprint

Hispanic Americans
Health
Lipids
Single Nucleotide Polymorphism
Genes
Genome-Wide Association Study
Cholesterol
Statistical Models
Gene Frequency
LDL Cholesterol
HDL Cholesterol
Population
Genome

Keywords

  • Ancestry
  • Cholesterol
  • Genetics
  • HDL
  • Hispanic/Latino
  • LDL
  • Triglycerides

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Graff, M., Emery, L. S., Justice, A. E., Parra, E., Below, J. E., Palmer, N. D., ... North, K. E. (2017). Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos. Lipids in Health and Disease, 16(1), [200]. https://doi.org/10.1186/s12944-017-0591-6

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.

In: Lipids in Health and Disease, Vol. 16, No. 1, 200, 12.10.2017.

Research output: Contribution to journalArticle

Graff, M, Emery, LS, Justice, AE, Parra, E, Below, JE, Palmer, ND, Gao, C, Duan, Q, Valladares-Salgado, A, Cruz, M, Morrison, AC, Boerwinkle, E, Whitsel, EA, Kooperberg, C, Reiner, A, Li, Y, Rodriguez, CJ, Talavera, GA, Langefeld, CD, Wagenknecht, LE, Norris, JM, Taylor, KD, Papanicolaou, G, Kenny, E, Loos, RJF, Chen, YDI, Laurie, C, Sofer, T & North, KE 2017, 'Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos', Lipids in Health and Disease, vol. 16, no. 1, 200. https://doi.org/10.1186/s12944-017-0591-6
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. In: Lipids in Health and Disease. 2017 ; Vol. 16, No. 1.
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abstract = "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.",
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T1 - Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos

AU - Graff, Mariaelisa

AU - Emery, Leslie S.

AU - Justice, Anne E.

AU - Parra, Esteban

AU - Below, Jennifer E.

AU - Palmer, Nicholette D.

AU - Gao, Chuan

AU - Duan, Qing

AU - Valladares-Salgado, Adan

AU - Cruz, Miguel

AU - Morrison, Alanna C.

AU - Boerwinkle, Eric

AU - Whitsel, Eric A.

AU - Kooperberg, Charles

AU - Reiner, Alex

AU - Li, Yun

AU - Rodriguez, Carlos Jose

AU - Talavera, Gregory A.

AU - Langefeld, Carl D.

AU - Wagenknecht, Lynne E.

AU - Norris, Jill M.

AU - Taylor, Kent D.

AU - Papanicolaou, George

AU - Kenny, Eimear

AU - Loos, Ruth J.F.

AU - Chen, Yii Der Ida

AU - Laurie, Cathy

AU - Sofer, Tamar

AU - North, Kari E.

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N2 - 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.

AB - 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.

KW - Ancestry

KW - Cholesterol

KW - Genetics

KW - HDL

KW - Hispanic/Latino

KW - LDL

KW - Triglycerides

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