Quality control and conduct of genome-wide association meta-analyses.
Winkler TWDepartment of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
Day FRMedical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Croteau-Chonka DC1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Wood ARGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Locke AEDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Mägi REstonian Genome Center, University of Tartu, Tartu, Estonia.
Ferreira TWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Fall T1] Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Graff MDepartment of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Justice AEDepartment of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Luan JMedical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Gustafsson SDepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Randall JCWellcome Trust Sanger Institute, Cambridge, UK.
Vedantam S1] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Workalemahu TDepartment of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
Kilpeläinen TOThe Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Scherag A1] Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital of Essen, University of Duisburg-Essen, Essen, Germany. [2] Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
Esko T1] Estonian Genome Center, University of Tartu, Tartu, Estonia. [2] Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [4] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Kutalik Z1] Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland. [2] Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. [3] Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Heid IM1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany. [2].
Loos RJ1] The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [4].
English
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.