Bayesian Approach to Sex-specific Mendelian Randomization Analysis

Nuzulul Kurniansyah Co-Author
Department of Medicine, Brigham and Women’s Hospital
 
Daniel F Levey Co-Author
Department of Psychiatry, Yale University School of Medicine
 
Joel Gelernter Co-Author
Department of Psychiatry, Yale University School of Medicine
 
Jennifer Huffman Co-Author
Center for Population Genomics, MAVERIC, VA Boston Healthcare System, Boston,
 
Kelly Cho Co-Author
Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare
 
Peter Wilson Co-Author
Division of Cardiology, Department of Medicine, Emory University School of Medicine
 
Daniel Gottlieb Co-Author
Division of Sleep Medicine, Harvard Medical School
 
Kenneth Rice Co-Author
University of Washington
 
Tamar Sofer Co-Author
Beth Israel Deaconess Medical Center
 
Yu-Jyun Huang First Author
Beth Israel Deaconess Medical Center
 
Yu-Jyun Huang Presenting Author
Beth Israel Deaconess Medical Center
 
Monday, Aug 5: 8:45 AM - 8:50 AM
3392 
Contributed Speed 
Oregon Convention Center 
Mendelian randomization (MR) analysis is widely used in genetic epidemiology to estimate the causal effect of a risk factor on an outcome of interest. Increasing evidence shows the importance of sex differences in health and disease mechanisms. However, research on sex-specific causal effects is lacking due to limited sex-specific GWASs. Motivated by GWASs from the Million Veteran Program, in which only 10% of individuals are female, a major limitation to MR analyses is weak IVs, which manifest as poor variant-exposure effect estimates that lead to unstable causal effect estimates. We propose a Bayesian framework to stabilize female exposure GWAS effect sizes by borrowing information from the male population. By specifying a particular prior distribution on female exposure GWAS effect sizes, we demonstrate two special cases of posterior means, including the inverse variance-weighted meta-analysis and the adaptive weight approach. We perform a series of simulation studies to examine the performance of our proposed Bayesian approach in MR analysis. Finally, we apply the proposed method to estimate the causal effects of sleep phenotypes on cardiovascular-related diseases

Keywords

MR analysis

Bayesian framework

Sex-specific causal effect 

Main Sponsor

Section on Statistics in Genomics and Genetics