Gene Association Analysis of Quantitative Trait Based on Functional Linear Regression Model with Local Sparse Estimator

Abstract

Functional linear regression models have been widely used in the gene association analysis of complex traits. These models retain all the genetic information in the data and take full advantage of spatial information in genetic variation data, which leads to brilliant detection power. However, the significant association signals identified by the high-power methods are not all the real causal SNPs, because it is easy to regard noise information as significant association signals, leading to a false association. In this paper, a method based on the sparse functional data association test (SFDAT) of gene region association analysis is developed based on a functional linear regression model with local sparse estimation. The evaluation indicators CSR and DL are defined to evaluate the feasibility and performance of the proposed method with other indicators. Simulation studies show that: (1) SFDAT performs well under both linkage equilibrium and linkage disequilibrium simulation; (2) SFDAT performs successfully for gene regions (including common variants, low-frequency variants, rare variants and mix variants); (3) With power and type I error rates comparable to OLS and Smooth, SFDAT has a better ability to handle the zero regions. The Oryza sativa data set is analyzed by SFDAT. It is shown that SFDAT can better perform gene association analysis and eliminate the false positive of gene localization. This study showed that SFDAT can lower the interference caused by noise while maintaining high power. SFDAT provides a new method for the association analysis between gene regions and phenotypic quantitative traits.