Quality control and conduct of genome-wide association meta-analyses.
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.
Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
Thomas W
TW
Winkler
Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Felix R
0000000337897651
FR
Day
1] 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.
Damien C
DC
Croteau-Chonka
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Andrew R
AR
Wood
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Adam E
AE
Locke
Estonian Genome Center, University of Tartu, Tartu, Estonia.
Reedik
R
Mägi
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Teresa
T
Ferreira
1] 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.
Tove
T
Fall
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Mariaelisa
M
Graff
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Anne E
AE
Justice
Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Jian'an
J
Luan
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Stefan
S
Gustafsson
Wellcome Trust Sanger Institute, Cambridge, UK.
Joshua C
JC
Randall
1] 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.
Sailaja
S
Vedantam
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
Tsegaselassie
T
Workalemahu
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tuomas O
TO
Kilpeläinen
1] 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.
André
A
Scherag
1] 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.
Tonu
T
Esko
1] 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.
Zoltán
Z
Kutalik
1] Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany. [2].
Iris M
IM
Heid
1] 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].
Ruth J F
RJ
Loos
D055106:Genome-Wide Association Study / Q000379:methods*; D015201:Meta-Analysis as Topic; D011786:Quality Control; D012984:Software