Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

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

doi:10.1093/hmg/ddw358

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Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

Journal article

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Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

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, …

Human molecular genetics, Vol.25(24), pp.5500-5512

12/15/2016

DOI: 10.1093/hmg/ddw358

PMCID: PMC5721937

PMID: 28426890

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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.

Genome-Wide Association Study

Hispanic Americans - genetics

Lipids - genetics

Lipoprotein Lipase - genetics

Humans

Asian Continental Ancestry Group - genetics

African Americans - genetics

Male

Cholesterol, HDL - genetics

Cholesterol, LDL - genetics

Indians, North American - genetics

Female

ATP Binding Cassette Transporter, Subfamily G, Member 8 - genetics

Triglycerides - genetics

Apolipoprotein A-V - genetics

Details

Title: Subtitle: Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci
Creators: Niha Zubair - Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Mariaelisa Graff - Department of Epidemiology
Jose Luis Ambite - Department of Computer Science, University of Southern California, Los Angeles, CA, USA
William S Bush - Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
Gleb Kichaev - Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA
Yingchang Lu - The Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA
Ani Manichaikul - Center for Public Health Genomics and Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, USA
Wayne H-H Sheu - Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Devin Absher - HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
Themistocles L Assimes - Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Suzette J Bielinski - Division of Epidemiology, Mayo Clinic, Rochester MN, USA
Erwin P Bottinger - The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA
Petra Buzkova - Department of Biostatistics, University of Washington, Seattle, WA, USA
Lee-Ming Chuang - National Taiwan University
Ren-Hua Chung
Barbara Cochran - Genetic Laboratory at the University of Texas Health Science Center, University of Texas, Houston, TX, USA
Logan Dumitrescu - Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA
Omri Gottesman - The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA
Jeffrey W Haessler - WHI Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Christopher Haiman - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Gerardo Heiss - Department of Epidemiology
Chao A Hsiung - Institute of Population Health Sciences, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan
Yi-Jen Hung - Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Chii-Min Hwu - School of Medicine, National Yang-Ming University, Taipei, Taiwan
Jyh-Ming J Juang - Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
Loic Le Marchand - Cancer Epidemiology Program, University of Hawai'i Cancer Center, University of Hawai'i at Manoa, Honolulu, Hawai'i. USA
I-Te Lee - Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Wen-Jane Lee - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
Li-An Lin - Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Danyu Lin - Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Shih-Yi Lin - Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Rachel H Mackey - Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
Lisa W Martin - Cardiology Division, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA
Bogdan Pasaniuc - Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA
Ulrike Peters - Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Irene Predazzi - Knight Cardiovascular Institute, Center for Preventative Cardiology, Oregon Health & Science University, Portland, OR, USA
Thomas Quertermous - Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Alex P Reiner - Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Jennifer Robinson - Department of Epidemiology, University of Iowa, Iowa City, Iowa, USA
Jerome I Rotter - Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
Kelli K Ryckman - Department of Epidemiology, University of Iowa, Iowa City, Iowa, USA
Pamela J Schreiner - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA
Eli Stahl - Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Ran Tao - Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Michael Y Tsai - Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Lindsay L Waite - HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
Tzung-Dau Wang - Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
Steven Buyske - Department of Statistics & Biostatistics, Rutgers University, Piscataway, NJ, USA
Yii-Der Ida Chen - Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
Iona Cheng - Cancer Prevention Institute of California, Fremont, CA, USA
Dana C Crawford - Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
Ruth J F Loos - The Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA
Stephen S Rich - Center for Public Health Genomics and Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, USA
Myriam Fornage - Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Kari E North - Department of Epidemiology
Charles Kooperberg - Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Cara L Carty - Center for Translational Science, George Washington University, Children's National Medical Center, Washington, DC, USA
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.25(24), pp.5500-5512
Publisher: England
DOI: 10.1093/hmg/ddw358
PMID: 28426890
PMCID: PMC5721937
ISSN: 1460-2083
eISSN: 1460-2083
Grant note: U01 HG004798 / NHGRI NIH HHS U01 HG007417 / NHGRI NIH HHS U01 HG007419 / NHGRI NIH HHS U01 HG004802 / NHGRI NIH HHS U01 HG004803 / NHGRI NIH HHS U01 HG004790 / NHGRI NIH HHS UL1 TR001881 / NCATS NIH HHS T32 HL007055 / NHLBI NIH HHS S10 OD018522 / NIH HHS UL1 TR000124 / NCATS NIH HHS U01 HG004801 / NHGRI NIH HHS P30 DK063491 / NIDDK NIH HHS
Language: English
Date published: 12/15/2016
Academic Unit: Stead Family Department of Pediatrics; Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9983995126302771

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