Multi-resolution localization of causal variants across the genome.

Published in Nature Communications, 2020

Abstract

We present KnockoffZoom, a flexible method for the genetic mapping of complex traits atmultiple resolutions.KnockoffZoomlocalizes causal variants by testing the conditional asso-ciations of genetic segments of decreasing width while provably controlling the false discovery rate using artificial genotypes as negative controls. Our method is equally valid for quan-titative and binary phenotypes,making no assumptions about their genetic architectures.Instead, we rely on well-established genetic models of linkage disequilibrium. We demonstrate that our method can detect more associations than mixed effects models and achievefine-mapping precision, at comparable computational cost. Lastly, we apply KnockoffZoomto data from 350k subjects in the UK Biobank and report many new findings.

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