Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci
Year: 2016
Type: article
Study design: Observational Study
Abstract: Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddw358
Authors: Niha Zubair, Mariaelisa Graff, Jose Luis Ambite, William S. Bush, Gleb Kichaev, Yingchang Lu, Ani Manichaikul, Wayne H-H. Sheu, Devin Absher, Themistocles L. Assimes, Suzette J. Bielinski, Erwin P. Bottinger, Petra Buzkova, Lee-Ming Chuang, Ren-Hua Chung, Barbara Cochran, Logan Dumitrescu, Omri Gottesman, Jeffrey W. Haessler, Christopher Haiman, Gerardo Heiss, Chao A. Hsiung, Yi-Jen Hung, Chii-Min Hwu, Jyh-Ming J. Juang, Loic Le Marchand, I-Te Lee, Wen-Jane Lee, Li-An Lin, Danyu Lin, Shih-Yi Lin, Rachel H. Mackey, Lisa W. Martin, Bogdan Pasaniuc, Ulrike Peters, Irene Predazzi, Thomas Quertermous, Alex P. Reiner, Jennifer Robinson, Jerome I. Rotter, Kelli K. Ryckman, Pamela J. Schreiner, Eli Stahl, Ran Tao, Michael Y. Tsai, Lindsay L. Waite, Tzung-Dau Wang, Steven Buyske, Yii-Der Ida Chen, Iona Cheng, Dana C. Crawford, Ruth J.F. Loos, Stephen S. Rich, Myriam Fornage, Kari E. North, Charles Kooperberg, Cara L. Carty
Institutions: Fred Hutch Cancer Center, University of Southern California, Case Western Reserve University, University of California, Los Angeles, Icahn School of Medicine at Mount Sinai, University of Virginia, Taichung Veterans General Hospital, HudsonAlpha Institute for Biotechnology, Stanford Medicine, Stanford University, Mayo Clinic, University of Washington, National Taiwan University, National Health Research Institutes, The University of Texas Health Science Center at Houston, Vanderbilt University, Women's Health Initiative, Tri-Service General Hospital, National Defense Medical Center, National Yang Ming University, National Taiwan University Hospital, University of Hawaiʻi at Mānoa, University of Hawaii System, University of Hawaii Cancer Center, University of North Carolina at Chapel Hill, University of Pittsburgh, George Washington University, Oregon Health & Science University, University of Iowa, Harbor–UCLA Medical Center, University of Minnesota, Rutgers, The State University of New Jersey, Cancer Prevention Institute of California, Children's National
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: Epidemiology of putative genuine genetic variant: The Women's Health Intiative, G2215229, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, G3809286577, G3976675028, G4302802884, G4401737188, G5363869159, G7978962292, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G9000007515
OpenAlex ID: W2589014554