Statistical Models for Analyzing X-Chromosome Data

• Activity Number: 106
• Type: Invited
• Date/Time: Monday, August 10, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Sanjay Shete*
• Companies: MD Anderson Cancer Center
• Keywords: X-chromosome ; genetics ; association ; XCI ; epidemiology ; cancer

Abstract

X-chromosome inactivation (XCI) is the process in which one of the two copies of the X-chromosome in females is randomly inactivated to achieve the dosage compensation of X-linked genes between males and females. However, studies have shown that skewed or nonrandom XCI is a biological plausibility wherein more than 75% of cells have the same allele inactive. Also, some of the X-chromosome genes escape XCI, i.e., both alleles are active in all cells. Current statistical tests for X-chromosome association studies can either account for random XCI or escape from XCI. Because the true XCI process is unknown and differs across different regions on the X-chromosome, we proposed a unified approach of maximizing likelihood ratio over all biological possibilities: random XCI, skewed XCI, and escape from XCI. The results showed that the proposed approach has higher powers in the scenarios where XCI is skewed while losing some power in scenarios where XCI is random or XCI is escaped, with well-controlled type I errors.