title: Genetic associations with lipoprotein subfraction measures differ by ethnicity in the multi-ethnic study of atherosclerosis (MESA).
abstract: A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European-Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African-Americans (AAs), 1450 Hispanic-Americans (HAs), and 775 Chinese-Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study center, and genetic ancestry (based on principal components), and additionally adjusted for Mexican/Non-Mexican status in HAs. A false discovery rate correction was applied separately within the results for each ethnicity to correct for multiple testing. Power calculations revealed that we did not have the power for SNP-based measures of association, so we analyzed phenotype-specific genetic risk scores (GRSs), constructed as in the original genome-wide analysis. We successfully replicated all 15 GRS-lipoprotein associations in 2527 EAs. Among the 15 significant GRS-lipoprotein associations in EAs, 11 were significant in AAs, 13 in HAs, and 1 in CHNs. Further analyses revealed that ethnicity differences could not be explained by differences in linkage disequilibrium, lipid lowering drugs, diabetes, or gender. Our study emphasizes the importance of ethnicity (here indexing genetic ancestry) in genetic risk for CVD and highlights the need to identify ethnicity-specific genetic variants associated with CVD risk.
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Health, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA.|Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichukal
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, Aurora, CO, 80045, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: Divisions of Preventive Medicine and Cardiovascular Medicine Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.|The Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC), 28029, Madrid, Spain.|IMDEA Food, 28049, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Pajewski
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.affiliation: Los Angeles Biomedical Research Institute and Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA.|Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Sale
authors.affiliation: Department of Mathematical and Statistical Sciences, Human Medical Genetics and Genomics Program, Department of Biostatistics & Informatics, University of Colorado Denver, Denver, CO, 80204, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Santorico
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine and Epidemiology, University of Washington, Seattle, WA, 98195, USA.|The New York Academy of Medicine, New York, NY, 10029, USA.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: College of Public Health, University of Kentucky, Lexington, KY, 40508, USA.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA.|Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rich
authors.affiliation: Department of Pediatrics, USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, 77030, USA. Lekki.Wood@Gmail.com.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000145:classification*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D008074:Lipoproteins