A rapid epistatic mixed-model association analysis by linear retransformations of genomic estimated values

作者：Ning, Chao; Wang, Dan; Kang, Huimin; Mrode, Raphael; Zhou, Lei; Xu, Shizhong; Liu, Jian-Feng^*

来源：Bioinformatics, 2018, 34(11): 1817-1825.

DOI：10.1093/bioinformatics/bty017

• TRAIT VARIATION
• PREDICTION

Motivation: Epistasis provides a feasible way for probing potential genetic mechanism of complex traits. However, time-consuming computation challenges successful detection of interaction in practice, especially when linear mixed model (LMM) is used to control type I error in the presence of population structure and cryptic relatedness.
Results: A rapid epistatic mixed-model association analysis (REMMA) method was developed to overcome computational limitation. This method first estimates individuals' epistatic effects by an extended genomic best linear unbiased prediction (EG-BLUP) model with additive and epistatic kinship matrix, then pairwise interaction effects are obtained by linear retransformations of individuals' epistatic effects. Simulation studies showed that REMMA could control type I error and increase statistical power in detecting epistatic QTNs in comparison with existing LMM-based FaST-LMM. We applied REMMA to two real datasets, a mouse dataset and the Wellcome Trust Case Control Consortium (WTCCC) data. Application to the mouse data further confirmed the performance of REMMA in controlling type I error. For the WTCCC data, we found most epistatic QTNs for type 1 diabetes (T1D) located in a major histocompatibility complex (MHC) region, from which a large interacting network with 12 hub genes (interacting with ten or more genes) was established.

• 出版日期2018-6-1
• 单位中国农业大学