Quality control and conduct of genome-wide association meta-analyses.
Winkler TW., Day FR., Croteau-Chonka DC., Wood AR., Locke AE., Mägi R., Ferreira T., Fall T., Graff M., Justice AE., Luan J., Gustafsson S., Randall JC., Vedantam S., Workalemahu T., Kilpeläinen TO., Scherag A., Esko T., Kutalik Z., Heid IM., Loos RJF., Genetic Investigation of Anthropometric Traits (GIANT) Consortium None.
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.