Date/Time
Date(s) - 24/01/2023
3:30 pm - 5:00 pm

Speaker: Lei Sun, University of Toronto

Title: Recent advances and new challenges to combat eXclusion in whole-genome studies

Abstract: The inclusion of the X chromosome in genome-wide association studies (GWAS) is known to be difficult due to multiple analytical challenges, particularly the uncertainty of X-inactivation, meaning one of the two X chromosomes in a female is randomly (or preferentially) silenced(i.e. dosage compensation). There is also the possibility of no X-inactivation(i.e. X-inactivation escape). To date, less than 1/3 of GWAS reported in the NHGRI-EBI GWAS catalog includes the X chromosome.

In this talk, I will first present an easy-to-implement association method that is robust to X-inactivation uncertainty, including skewed X-inactivation. I will then show evidence for sex differences in minor allele frequency (sdMAF), a previously under-appreciated phenomenon of the X chromosome, based on our recentan alyses of the highcoverage whole genome sequence data of the 1000 Genomes Project and gnomAD v3.1.2. To jointly analyze samples from multiple populations, I will present a new retrospective regression method to detect and compare sdMAF across populations.Finally, I will present our recent methodological work on testing for departure from Hardy-Weinberg equilibrium, including a novel regression-based method that includes the classical autosomal Pearson’s Chisquared test as a special case,and possible extensions to combat eXclusion of the X chromosome. 

This is joint work with Dr. Andrew Paterson, Prof. Radu Craiu, and several former and current trainees, including Dr. Bo Chen, Zhong Wang, and Dr. Lin Zhang.

Date/Time: Tuesday January 24, 2023, 3:30 – 5:00 

Location: MDCL 1115