Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study

Autoři: Yao Hu aff001;  Mariaelisa Graff aff002;  Jeffrey Haessler aff001;  Steven Buyske aff003;  Stephanie A. Bien aff001;  Ran Tao aff004;  Heather M. Highland aff002;  Katherine K. Nishimura aff001;  Niha Zubair aff001;  Yingchang Lu aff006;  Marie Verbanck aff006;  Austin T. Hilliard aff007;  Derek Klarin aff008;  Scott M. Damrauer aff011;  Yuk-Lam Ho aff014;  ;  Peter W. F. Wilson aff011;  Kyong-Mi Chang aff012;  Philip S. Tsao aff017;  Kelly Cho aff014;  Christopher J. O’Donnell aff014;  Themistocles L. Assimes aff017;  Lauren E. Petty aff005;  Jennifer E. Below aff005;  Ozan Dikilitas aff021;  Daniel J. Schaid aff022;  Matthew L. Kosel aff022;  Iftikhar J. Kullo aff021;  Laura J. Rasmussen-Torvik aff023;  Gail P. Jarvik aff024;  Qiping Feng aff025;  Wei-Qi Wei aff025;  Eric B. Larson aff026;  Frank D. Mentch aff027;  Berta Almoguera aff027;  Patrick M. Sleiman aff027;  Laura M. Raffield aff028;  Adolfo Correa aff029;  Lisa W. Martin aff030;  Martha Daviglus aff031;  Tara C. Matise aff003;  Jose Luis Ambite aff033;  Christopher S. Carlson aff001;  Ron Do aff006;  Ruth J. F. Loos aff006;  Lynne R. Wilkens aff034;  Loic Le Marchand aff034;  Chris Haiman aff035;  Daniel O. Stram aff035;  Lucia A. Hindorff aff036;  Kari E. North aff002;  Charles Kooperberg aff001;  Iona Cheng aff037;  Ulrike Peters aff001
Působiště autorů: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America aff001;  Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America aff002;  Department of Statistics and Biostatistics, Rutgers University, New Brunswick, New Jersey, United States of America aff003;  Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff004;  The Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff005;  The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America aff006;  Palo Alto Veterans Institute for Research, VA Palo Alto Health Care System, Palo Alto, California, United States of America aff007;  Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff008;  Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America aff009;  Boston VA Healthcare System, Boston, Massachusetts, United States of America aff010;  Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, United States of America aff011;  Corporal Michael Crescenz VA Medical Center, Philadelphia, Pennsylvania, United States of America aff012;  Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff013;  Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, United States of America aff014;  Atlanta VA Medical Center, Decatur, Georgia, United States of America aff015;  Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff016;  Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America aff017;  VA Palo Alto Health Care System, Palo Alto, California, United States of America aff018;  Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America aff019;  Department of Epidemiology, Human Genetics & Environmental Sciences, University of Texas School of Public Health, Houston, Texas, United States of America aff020;  Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, United states of America aff021;  Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America aff022;  Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America aff023;  Department of Medicine, University of Washington Medical Center, Seattle, Washington, United States of America aff024;  Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff025;  Kaiser Permanente Washington Health Research Institute, Seattle, Washington, United States of America aff026;  Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America aff027;  Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America aff028;  Departments of Medicine, Pediatrics, and Population Health Science, University of Mississippi Medical Center, Jackson, Mississippi, United States of America aff029;  School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, United States of America aff030;  Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois, United States of America aff031;  Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America aff032;  Information Sciences Institute, University of Southern California, Marina del Rey, California, United States of America aff033;  Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America aff034;  Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America aff035;  Division of Genomic Medicine, NIH National Human Genome Research Institute, Bethesda, Maryland, United States of America aff036;  Cancer Prevention Institute of California, Fremont, California, United States of America aff037
Vyšlo v časopise: Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008684
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008684


Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S. minority groups. We performed genome-wide association analyses for four lipid traits in over 45,000 ancestrally diverse participants from the Population Architecture using Genomics and Epidemiology (PAGE) Study, followed by a meta-analysis with several European ancestry studies. We identified nine novel lipid loci, five of which showed evidence of replication in independent studies. Furthermore, we discovered one novel gene in a PrediXcan analysis, minority-specific independent signals at eight previously reported loci, and potential functional variants at two known loci through fine-mapping. Systematic examination of known lipid loci revealed smaller effect estimates in African American and Hispanic ancestry populations than those in Europeans, and better performance of polygenic risk scores based on minority-specific effect estimates. Our findings provide new insight into the genetic architecture of lipid traits and highlight the importance of conducting genetic studies in diverse populations in the era of precision medicine.

Klíčová slova:

Europe – Genetic loci – Genome-wide association studies – Hispanic people – Lipids – Metaanalysis – Population genetics – Trait locus analysis


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