Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1817-1825 |
| Number of pages | 9 |
| Journal | Bioinformatics |
| Volume | 34 |
| Issue number | 11 |
| Early online date | 12 Jan 2018 |
| DOIs | |
| Publication status | Print publication - 1 Jun 2018 |
| Externally published | Yes |
