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An Efficient Multiple-Testing Adjustment for eQTL Studies that Accounts for Linkage Disequilibrium between Variants.

Davis, Joe R; Fresard, Laure; Knowles, David A; Pala, Mauro; Bustamante, Carlos D; Battle, Alexis; Montgomery, Stephen B.
Am J Hum Genet; 98(1): 216-24, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26749306
Methods for multiple-testing correction in local expression quantitative trait locus (cis-eQTL) studies are a trade-off between statistical power and computational efficiency. Bonferroni correction, though computationally trivial, is overly conservative and fails to account for linkage disequilibrium between variants. Permutation-based methods are more powerful, though computationally far more intensive. We present an alternative correction method called eigenMT, which runs over 500 times faster than permutations and has adjusted p values that closely approximate empirical ones. To achieve this speed while also maintaining the accuracy of permutation-based methods, we estimate the effective number of independent variants tested for association with a particular gene, termed Meff, by using the eigenvalue decomposition of the genotype correlation matrix. We employ a regularized estimator of the correlation matrix to ensure Meff is robust and yields adjusted p values that closely approximate p values from permutations. Finally, using a common genotype matrix, we show that eigenMT can be applied with even greater efficiency to studies across tissues or conditions. Our method provides a simpler, more efficient approach to multiple-testing correction than existing methods and fits within existing pipelines for eQTL discovery.
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