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Quality control and conduct of genome-wide association meta-analyses

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Authors:
  • Winkler, Thomas W ;
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    Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg
  • Day, Felix R ;
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    Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
  • Croteau-Chonka, Damien C ;
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    Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Wood, Andrew R ;
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    Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
  • Locke, Adam E ;
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    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Mägi, Reedik ;
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    University of Tartu
  • Ferreira, Teresa ;
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    University of Oxford
  • Fall, Tove ;
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    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University
  • Graff, Mariaelisa ;
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    Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Justice, Anne E ;
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    Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Luan, Jian'an ;
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    Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
  • Gustafsson, Stefan ;
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    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University
  • Randall, Joshua C ;
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    Wellcome Trust Sanger Institute
  • Vedantam, Sailaja ;
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    Boston Children's Hospital, Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research
  • Workalemahu, Tsegaselassie ;
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    Harvard School of Public Health
  • Kilpeläinen, Tuomas ;
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    Orcid logo0000-0002-8349-3028
    Human Genomics and Metagenomics in Metabolism, NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Scherag, André ;
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    University of Duisburg-Essen
  • Esko, Tonu ;
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    Boston Children's Hospital, Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research
  • Kutalik, Zoltán ;
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    Department of Medical Genetics, University of Lausanne
  • Heid, Iris M ;
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    Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg
  • Loos, Ruth J F
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    The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
DOI:
10.1038/nprot.2014.071
Abstract:
Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
Type:
Journal article
Language:
English
Published in:
Nature Protocols (online), 2014, Vol 9, Issue 5, p. 1192-1212
Keywords:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Genome-Wide Association Study; Meta-Analysis as Topic; Quality Control; Software
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2014
Scientific Level:
Scientific
ID:
266902305

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