A Fast and Efficient Likelihood Approach for Genome-Wide Mediation Analysis Under Extreme Phenotype Sequencing

• Activity Number: 55 - Statistical methods for data from single cell technologies
• Type: Contributed
• Date/Time: Sunday, August 8, 2021 : 3:30 PM to 5:20 PM
• Sponsor: Section on Statistics in Genomics and Genetics
• Author(s): Janaka S. S. Liyanage* and Guolian Kang
• Companies: St. Jude Children’s Research Hospital and St. Jude Children’s Research Hospital
• Keywords: Mediation effect; mediation analysis; extreme phenotype sequencing; genome-wide association studies; next generation sequencing studies

Abstract

Due to many advantages of statistics methods, extreme phenotype sequencing (EPS) design is a rapidly emerging study design in modern epidemiological and clinical studies in investigating the involvement of genetic variations in underlying disease mechanisms. However, investigation of the mediation effect of genetic variants in disease leading causal pathways is strictly restrictive under the EPS design as it implements non-random extreme tails sampling process. In this paper, we propose a likelihood approach for testing the mediation effect of genetic variants through continuous and binary mediators on a continuous phenotype under the EPS design. Besides implementing in EPS design, it also can be utilized as a general mediation analysis methodology under the general random sampling framework. Simulations and real data applications of a genome-wide association study of benign ethnic neutropenia and a candidate-gene study of neurocognition in patients with sickle cell disease demonstrate the superiority of the proposed approach under the EPS design over widely used mediation analysis procedures, while demonstrating compatible capabilities under the general random sampling framework.