Multikernel linear mixed models for complex phenotype prediction.
Linear mixed models (LMMs) and their extensions have recently become the method of choice in phenotype prediction for complex traits. However, LMM use to date has typically been limited by assuming simple genetic architectures. Here, we present multikernel linear mixed model (MKLMM), a predictive modeling framework that extends the standard LMM using multiple-kernel machine learning approaches. MKLMM can model genetic interactions and is particularly suitable for modeling complex local interactions between nearby variants. We additionally present MKLMM-Adapt, which automatically infers interaction types across multiple genomic regions. In an analysis of eight case-control data sets from the Wellcome Trust Case Control Consortium and more than a hundred mouse phenotypes, MKLMM-Adapt consistently outperforms competing methods in phenotype prediction. MKLMM is as computationally efficient as standard LMMs and does not require storage of genotypes, thus achieving state-of-the-art predictive power without compromising computational feasibility or genomic privacy.
Department of Statistics and Operations Research, School of Mathematical Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel; Computer Science Department, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Omer
O
Weissbrod
Computer Science Department, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Dan
D
Geiger
Department of Statistics and Operations Research, School of Mathematical Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel;
Saharon
S
Rosset
D000465:Algorithms; D000818:Animals; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003198:Computer Simulation; D006801:Humans; D016014:Linear Models; D051379:Mice; D008957:Models, Genetic; D010641:Phenotype; D012984:Software