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

Thomas W Winkler; Felix R Day; Damien C Croteau-Chonka; Andrew R Wood; Adam E Locke; Reedik Mägi; Teresa Ferreira; Tove Fall; Mariaelisa Graff; Anne E Justice; Jian'an Luan; Stefan Gustafsson; Joshua C Randall; Sailaja Vedantam; Tsegaselassie Workalemahu; Tuomas Kilpeläinen; André Scherag; Tonu Esko; Zoltán Kutalik; Iris M Heid; Ruth J F Loos; Genetic Investigation of Anthropometric Traits (GIANT) Consortium

doi:10.1038/nprot.2014.071

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

Thomas W Winkler, Felix R Day, Damien C Croteau-Chonka, Andrew R Wood, Adam E Locke, Reedik Mägi, Teresa Ferreira, Tove Fall, Mariaelisa Graff, Anne E Justice, Jian'an Luan, Stefan Gustafsson, Joshua C Randall, Sailaja Vedantam, Tsegaselassie Workalemahu, Tuomas Kilpeläinen, André Scherag, Tonu Esko, Zoltán Kutalik, Iris M HeidRuth J F Loos, Genetic Investigation of Anthropometric Traits (GIANT) Consortium

182 Citations (Scopus)

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.

Original language	English
Journal	Nature Protocols (Online)
Volume	9
Issue number	5
Pages (from-to)	1192-1212
Number of pages	21
ISSN	1750-2799
DOIs	https://doi.org/10.1038/nprot.2014.071
Publication status	Published - May 2014

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Winkler, T. W., Day, F. R., Croteau-Chonka, D. C., Wood, A. R., Locke, A. E., Mägi, R., Ferreira, T., Fall, T., Graff, M., Justice, A. E., Luan, J., Gustafsson, S., Randall, J. C., Vedantam, S., Workalemahu, T., Kilpeläinen, T., Scherag, A., Esko, T., Kutalik, Z., ... Genetic Investigation of Anthropometric Traits (GIANT) Consortium (2014). Quality control and conduct of genome-wide association meta-analyses. Nature Protocols (Online), 9(5), 1192-1212. https://doi.org/10.1038/nprot.2014.071

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, T, Scherag, A, Esko, T, Kutalik, Z, Heid, IM, Loos, RJF & Genetic Investigation of Anthropometric Traits (GIANT) Consortium 2014, 'Quality control and conduct of genome-wide association meta-analyses', Nature Protocols (Online), vol. 9, no. 5, pp. 1192-1212. https://doi.org/10.1038/nprot.2014.071

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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.",

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

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