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H-MAGMA, inheriting a shaky statistical foundation, yields excess false positives

By Ronald J Yurko, Kathryn Roeder, Bernie Devlin, Max G'Sell

Posted 22 Aug 2020
bioRxiv DOI: 10.1101/2020.08.20.260224

The 'snp-wise mean model' of Multi-marker Analysis of GenoMic Annotation is often used to perform gene-level testing for association with disease and other phenotypes. This methodology, in turn, forms the foundation for H-MAGMA. Unfortunately, that foundation is unsound, with implications for H-MAGMA results published in Nature Neuroscience regarding genes associated with psychiatric disorders: e.g., only 125 of H-MAGMA's 275 reported discoveries for autism replicate when the foundation's flaws are corrected. ### Competing Interest Statement The authors have declared no competing interest.

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