Bayesian Approach to Sex-specific Mendelian Randomization Analysis

Abstract Number:

3392 

Submission Type:

Contributed Abstract 

Contributed Abstract Type:

Speed 

Participants:

Yu-Jyun Huang (1), Nuzulul Kurniansyah (2), Daniel F Levey (3), Joel Gelernter (3), Jennifer Huffman (4), Kelly Cho (4), Peter Wilson (5), Daniel Gottlieb (6), Kenneth Rice (7), Tamar Sofer (1)

Institutions:

(1) Beth Israel Deaconess Medical Center, Boston, MA, (2) Department of Medicine, Brigham and Women’s Hospital, Boston, MA, (3) Department of Psychiatry, Yale University School of Medicine, New Haven, CT, (4) MAVERIC, VA Boston Healthcare System, Boston, MA, (5) Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, (6) Division of Sleep Medicine, Harvard Medical School, Boston, MA, (7) University of Washington, Seattle, WA

Co-Author(s):

Nuzulul Kurniansyah  
Department of Medicine, Brigham and Women’s Hospital
Daniel F Levey  
Department of Psychiatry, Yale University School of Medicine
Joel Gelernter  
Department of Psychiatry, Yale University School of Medicine
Jennifer Huffman  
MAVERIC, VA Boston Healthcare System
Kelly Cho  
MAVERIC, VA Boston Healthcare System
Peter Wilson  
Division of Cardiology, Department of Medicine, Emory University School of Medicine
Daniel Gottlieb  
Division of Sleep Medicine, Harvard Medical School
Kenneth Rice  
University of Washington
Tamar Sofer  
Beth Israel Deaconess Medical Center

First Author:

Yu-Jyun Huang  
Beth Israel Deaconess Medical Center

Presenting Author:

Yu-Jyun Huang  
Beth Israel Deaconess Medical Center

Abstract Text:

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| | |

Sponsors:

Section on Statistics in Genomics and Genetics

Tracks:

Miscellaneous

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