H-MAGMA, inheriting a shaky statistical foundation, yields excess false positives
Ronald YurkoiD, Kathryn RoederiD, Bernie DevliniD, Max G’Sell
Abstract
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-MAGMAs 275 reported discoveries for autism replicate when the foundations flaws are corrected.
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