A multi-marker association method for genome-wide association studies without the need for population structure correction

一种无需进行群体结构校正的全基因组关联研究多标记关联方法

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作者:Jonas R Klasen, Elke Barbez, Lukas Meier, Nicolai Meinshausen, Peter Bühlmann, Maarten Koornneef, Wolfgang Busch, Korbinian Schneeberger

Abstract

All common genome-wide association (GWA) methods rely on population structure correction, to avoid false genotype-to-phenotype associations. However, population structure correction is a stringent penalization, which also impedes identification of real associations. Using recent statistical advances, we developed a new GWA method, called Quantitative Trait Cluster Association Test (QTCAT), enabling simultaneous multi-marker associations while considering correlations between markers. With this, QTCAT overcomes the need for population structure correction and also reflects the polygenic nature of complex traits better than single-marker methods. Using simulated data, we show that QTCAT clearly outperforms linear mixed model approaches. Moreover, using QTCAT to reanalyse public human, mouse and Arabidopsis GWA data revealed nearly all known and some previously undetected associations. Following up on the most significant novel association in the Arabidopsis data allowed us to identify a so far unknown component of root growth.

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