Analysis in Case-Control Sequencing Association Studies with Different Sequencing Depths

• Activity Number: 367
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Sixing Chen* and Xihong Lin
• Companies: Harvard School of Public Health and Harvard School of Public Health
• Keywords: Next generation sequencing ; Association studies ; Case control ; Sequencing depth ; Regression calibration

Abstract

With the advent of next-generation sequencing, investigators have access to more reliable genetic information. However, to conduct an entire study with next generation sequencing can still be prohibitively expensive. One potential remedy could be to combine next generation sequencing data from cases with publicly available sequencing data for controls, but there could be confounding due to differences in sequencing depths. We propose two regression calibration-based methods and consider maximum-likelihood for conducting association study with the aligned reads from cases and controls. The regression calibration method assumes no additional sources of confounding or matched cases and controls, while the likelihood-based method allows for adjusting for other covariates. All three methods control type I error and have comparable power to analysis conducted using the true genotype with sufficiently high but different sequencing depths. One of the regression calibration methods allows for analysis with standard variance estimate and software under certain circumstances.