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Research Article

Enhanced Statistical Tests for GWAS in Admixed Populations: Assessment using African Americans from CARe and a Breast Cancer Consortium

  • Bogdan Pasaniuc mail,

    bpasaniu@hsph.harvard.edu (BP); aprice@hsph.harvard.edu (ALP)

    Affiliations: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America

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  • Noah Zaitlen,

    Affiliations: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America

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  • Guillaume Lettre,

    Affiliations: Montreal Heart Institute, Montréal, Canada, Département de Médecine, Université de Montréal, Montréal, Canada

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  • Gary K. Chen,

    Affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America

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  • Arti Tandon,

    Affiliations: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

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  • W. H. Linda Kao,

    Affiliations: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, United States of America

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  • Ingo Ruczinski,

    Affiliation: Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America

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  • Myriam Fornage,

    Affiliation: Institute of Molecular Medicine and Division of Epidemiology, School of Public Health, University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America

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  • David S. Siscovick,

    Affiliations: Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America

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  • Xiaofeng Zhu,

    Affiliation: Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America

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  • Emma Larkin,

    Affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University, Nashville, Tennessee, United States of America

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  • Leslie A. Lange,

    Affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America

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  • L. Adrienne Cupples,

    Affiliation: Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America

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  • Qiong Yang,

    Affiliation: Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America

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  • Ermeg L. Akylbekova,

    Affiliation: Jackson Heart Study, Jackson State University, Jackson, Mississippi, United States of America

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  • Solomon K. Musani,

    Affiliation: University of Mississippi Medical Center, Jackson, Mississippi, United States of America

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  • Jasmin Divers,

    Affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina, United States of America

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  • Joe Mychaleckyj,

    Affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America

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  • Mingyao Li,

    Affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America

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  • George J. Papanicolaou,

    Affiliation: National Heart, Lung, and Blood Institute (NHLBI), Division of Cardiovascular Sciences, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Robert C. Millikan,

    Affiliations: Department of Epidemiology, Gillings School of Global Public Health Chapel Hill, North Carolina, United States of America, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America

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  • Christine B. Ambrosone,

    Affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, United States of America

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  • Esther M. John,

    Affiliations: Northern California Cancer Center, Fremont, California, United States of America, Stanford University School of Medicine and Stanford Cancer Center, Stanford, California, United States of America

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  • Leslie Bernstein,

    Affiliation: Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, California, United States of America

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  • Wei Zheng,

    Affiliations: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Nashville, Tennessee, United States of America, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America

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  • Jennifer J. Hu,

    Affiliation: Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida, United States of America

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  • Regina G. Ziegler,

    Affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America

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  • Sarah J. Nyante,

    Affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America

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  • Elisa V. Bandera,

    Affiliation: The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America

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  • Sue A. Ingles,

    Affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America

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  • Michael F. Press,

    Affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America

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  • Stephen J. Chanock,

    Affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America

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  • Sandra L. Deming,

    Affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Nashville, Tennessee, United States of America

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  • Jorge L. Rodriguez-Gil,

    Affiliation: Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida, United States of America

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  • Cameron D. Palmer,

    Affiliations: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America, Divisions of Genetics and Endocrinology and Program in Genomics, Children’s Hospital Boston, Boston, Massachusetts, United States of America

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  • Sarah Buxbaum,

    Affiliation: Jackson Heart Study, Jackson State University, Jackson, Mississippi, United States of America

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  • Lynette Ekunwe,

    Affiliation: Jackson Heart Study, Jackson State University, Jackson, Mississippi, United States of America

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  • Joel N. Hirschhorn,

    Affiliations: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, Divisions of Genetics and Endocrinology and Program in Genomics, Children’s Hospital Boston, Boston, Massachusetts, United States of America

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  • Brian E. Henderson,

    Affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America

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  • Simon Myers,

    Affiliation: Department of Statistics, University of Oxford, Oxford, United Kingdom

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  • Christopher A. Haiman,

    Affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America

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  • David Reich,

    Affiliations: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Nick Patterson,

    Affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America

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  • James G. Wilson,

    Affiliations: University of Mississippi Medical Center, Jackson, Mississippi, United States of America, V. A. Medical Center, Jackson, Mississippi, United States of America

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  • Alkes L. Price mail

    bpasaniu@hsph.harvard.edu (BP); aprice@hsph.harvard.edu (ALP)

    Affiliations: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America

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  • Published: April 21, 2011
  • DOI: 10.1371/journal.pgen.1001371

About the Authors

Bogdan Pasaniuc, Noah Zaitlen, Alkes L. Price
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
Bogdan Pasaniuc, Noah Zaitlen, Alkes L. Price
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America
Bogdan Pasaniuc, Noah Zaitlen, Arti Tandon, Cameron D. Palmer, Joel N. Hirschhorn, David Reich, Nick Patterson, Alkes L. Price
Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America
Guillaume Lettre
Montreal Heart Institute, Montréal, Canada
Guillaume Lettre
Département de Médecine, Université de Montréal, Montréal, Canada
Gary K. Chen, Sue A. Ingles, Michael F. Press, Brian E. Henderson, Christopher A. Haiman
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America
Arti Tandon, Joel N. Hirschhorn, David Reich
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
W. H. Linda Kao
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America
W. H. Linda Kao
Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, United States of America
Ingo Ruczinski
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
Myriam Fornage
Institute of Molecular Medicine and Division of Epidemiology, School of Public Health, University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America
David S. Siscovick
Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America
David S. Siscovick
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America
Xiaofeng Zhu
Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
Emma Larkin
Department of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University, Nashville, Tennessee, United States of America
Leslie A. Lange
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America
L. Adrienne Cupples, Qiong Yang
Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America
Ermeg L. Akylbekova, Sarah Buxbaum, Lynette Ekunwe
Jackson Heart Study, Jackson State University, Jackson, Mississippi, United States of America
Solomon K. Musani, James G. Wilson
University of Mississippi Medical Center, Jackson, Mississippi, United States of America
Jasmin Divers
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina, United States of America
Joe Mychaleckyj
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America
Mingyao Li
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
George J. Papanicolaou
National Heart, Lung, and Blood Institute (NHLBI), Division of Cardiovascular Sciences, National Institutes of Health, Bethesda, Maryland, United States of America
Robert C. Millikan
Department of Epidemiology, Gillings School of Global Public Health Chapel Hill, North Carolina, United States of America
Robert C. Millikan, Sarah J. Nyante
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America
Christine B. Ambrosone
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, United States of America
Esther M. John
Northern California Cancer Center, Fremont, California, United States of America
Esther M. John
Stanford University School of Medicine and Stanford Cancer Center, Stanford, California, United States of America
Leslie Bernstein
Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, California, United States of America
Wei Zheng
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Nashville, Tennessee, United States of America
Wei Zheng
Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
Jennifer J. Hu, Jorge L. Rodriguez-Gil
Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida, United States of America
Regina G. Ziegler
Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Elisa V. Bandera
The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
Stephen J. Chanock
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Sandra L. Deming
Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Nashville, Tennessee, United States of America
Cameron D. Palmer, Joel N. Hirschhorn
Divisions of Genetics and Endocrinology and Program in Genomics, Children’s Hospital Boston, Boston, Massachusetts, United States of America
Simon Myers
Department of Statistics, University of Oxford, Oxford, United Kingdom
James G. Wilson
V. A. Medical Center, Jackson, Mississippi, United States of America

Corresponding Authors

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: BP NZ CAH DR NP JGW ALP. Performed the experiments: BP. Analyzed the data: BP AT ALP. Contributed reagents/materials/analysis tools: BP GL GKC WHLK IR MF DSS XZ EL LAL LAC QY ELA SKM JD JM ML GJP RCM CBA EMJ LB WZ JJH RGZ SJN EVB SAI MFP SJC SLD JLRG CDP SB LE JNH BEH SM CAH DR NP JGW ALP. Wrote the paper: BP NZ DR NP JGW ALP.