Join Dr. Razvan Romanescu from the Department of Community Health Sciences at the University of Manitoba for his talk on Thursday, November 19th about “Efficient Tests of Genetic Association for Rare Variants in Affected Sib Pairs”.


Next generation sequencing technologies have made it possible to investigate the role of rare variants (RVs) in disease etiology. Because RVs associated with disease susceptibility tend to be enriched in families with affected individuals, study designs based on affected sib pairs (ASP) can be more powerful than case-control studies. We construct tests of RV-set association in ASPs for single genomic regions as well as for multiple regions. Single-region tests can efficiently detect a gene region harboring susceptibility variants, while multiple-region extensions are meant to capture signals dispersed across a biological pathway, potentially as a result of locus heterogeneity. Within ascertained ASPs, the test statistics contrast the frequencies of duplicate rare alleles (usually appearing on a shared haplotype) against frequencies of a single rare allele copy (appearing on a non-shared haplotype); we call these allelic parity tests. Incorporation of minor allele frequency estimates from reference populations can markedly improve test efficiency. Under various genetic penetrance models, application of the tests in simulated ASP datasets demonstrates good type I error properties as well as power gains over approaches that regress ASP rare allele counts on sharing state. We discuss how to deal with the problem of misspecification of reference population allele frequencies, and outline future work. As proof of principle, we apply single- and multiple-region tests in a motivating study dataset consisting of whole exome sequencing of sisters ascertained with early onset breast cancer.

DATE: Thursday, November 19th, 2020

WHERE: Zoom (see below for more information)

WHEN: 2:30pm

If you wish to attend a Statistics Seminar please contact Po Yang ( or Leah Phillips ( from the U of M’s Statistics Department for more details and Zoom meeting information.