title: Genome-wide joint analysis of single-nucleotide variant sets and gene expression for hypertension and related phenotypes.
abstract: BACKGROUND
  With the advance of next-generation sequencing technologies, the study of rare variants in targeted genome regions or even the whole genome becomes feasible. Nevertheless, the massive amount of sequencing data brings great computational and statistical challenges for association analyses. Aside from sequencing variants, other high-throughput omic data (eg, gene expression data) also become available, and can be incorporated into association analysis for better modeling and power improvement. This motivates the need of developing computationally efficient and powerful approaches to model the joint associations of multilevel omic data with complex human diseases.
  
  
  METHODS
  A similarity-based weighted U approach is used to model the joint effect of sequencing variants and gene expression. Using a Mexican American sample provided by Genetic Analysis Workshop 19 (GAW19), we performed a whole-genome joint association analysis of sequencing variants and gene expression with systolic (SBP) and diastolic blood pressure (DBP) and hypertension (HTN) phenotypes.
  
  
  RESULTS
  The whole-genome joint association analysis was completed in 80 min on a high-performance personal computer with an i7 4700 CPU and 8 GB memory. Although no gene reached statistical significance after adjusting for multiple testing, some top-ranked genes attained a high significance level and may have biological plausibility to hypertension-related phenotypes.
  
  
  CONCLUSIONS
  The weighted U approach is computationally efficient for high-dimensional data analysis, and is capable of integrating multiple levels of omic data into association analysis. Through a real data application, we demonstrate the potential benefit of using the new approach for joint association analysis of sequencing variants and gene expression.
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824 USA.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Tong
authors.affiliation: Health Science Centre, University of North Texas, Fort Worth, TX 76107 USA.
authors.forename: Changshuai
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824 USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu