Identifying Genetic Variants for Obesity Incorporating Prior Insights: Quantile Regression with Insight Fusion for Ultra-high Dimensional Data

Abstract: Obesity is widely recognized as a critical and pervasive health concern. We strive to identify important genetic risk factors from hundreds of thousands of single nucleotide polymorphisms (SNPs) for obesity. We propose and apply a novel Quantile Regression with Insight Fusion (QRIF) approach that can integrate insights from established studies or domain knowledge to simultaneously select variables and modeling for ultra-high dimensional genetic data, focusing on high conditional quantiles of body mass index (BMI) that are of most interest. We discover interesting new SNPs and shed new light on a comprehensive view of the underlying genetic risk factors for different levels of BMI. This may potentially pave the way for more precise and targeted treatment strategies. The QRIF approach intends to balance the trade-off between the prior insights and the observed data while being robust to potential false information. We further establish the desirable asymptotic properties under the challenging non-differentiable check loss functions via Huber loss approximation and nonconvex SCAD penalty via local linear approximation. Finally, we develop an efficient algorithm for the QRIF approach. Our simulation studies further demonstrate its effectiveness.