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

Lipids in Health and Disease

Research

Anne E. Justice¹  Esteban Parra²  Nicholette D. Palmer³  Carl D. Langefeld⁴  Leslie S. Emery⁵  Cathy Laurie⁵  Jill M. Norris⁶  Mariaelisa Graff⁷  Kari E. North⁷  Eric A. Whitsel⁸  Eric Boerwinkle⁹  Alanna C. Morrison⁹  Qing Duan^1,10  Yun Li^1,10  Lynne E. Wagenknecht^1,11  Carlos Jose Rodriguez^1,11  Tamar Sofer^1,12  Charles Kooperberg^1,13  Alex Reiner^1,13  Eimear Kenny^1,14  Gregory A. Talavera^1,15  Yii-Der Ida Chen^1,16  Kent D. Taylor^1,16  Chuan Gao^1,17  George Papanicolaou^1,18  Ruth J. F. Loos^1,19  Adan Valladares-Salgado^2,20  Miguel Cruz^2,20  Jennifer E. Below^2,21 

[1] Biomedical and Translational Informatics, Geisinger Health, Danville, PA, USA;Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada;Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA;Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA;Department of Biostatistics, University of Washington, Seattle, WA, USA;Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA;Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA;Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA;Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Department of Medicine and Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA;Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA;Department of Medicine, Harvard Medical School, Boston, MA, USA;Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA, USA;Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Graduate School of Public Health, San Diego State University, San Diego, CA, USA;Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA;Molecular Genetics and Genomics Program, Wake Forest University School of Medicine, Winston-Salem, NC, USA;National Heart, Lung, and Blood Institute, 20892, Bethesda, MD, USA;The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Unidad de Investigacion Medica en Bioquimica, Hospital de Especialidades, CMNSXX1-IMSS, Mexico City, Mexico;Vanderbilt Genetics Institute, Vanderbuilt University, Nashville, TN, USA;

关键词: HDL;    LDL;    Triglycerides;    Cholesterol;    Genetics;    Ancestry;    Hispanic/Latino;   

DOI  :  10.1186/s12944-017-0591-6

 received in 2017-07-20, accepted in 2017-10-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDespite 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).MethodsWe 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.ResultsWe 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.ConclusionsThese results demonstrate that many loci associated with lipid levels are shared across populations.

【 授权许可】

CC BY   
© The Author(s). 2017