B0390
Title: The impact of the major histocompatibility complex region on causal discoveries in Mendelian randomization studies
Authors: Hui Guo - University of Manchester (United Kingdom) [presenting]
Abstract: Mendelian randomization (MR) is a well-established tool for causal inference. Genes in the major histocompatibility complex (MHC) region are associated with the risks of many diseases. It is hypothesized that the MHC region may play an important role in MR analysis which, however, has rarely been reported previously. The immune response to infections also hypothesized could be partly driven by MHC genes, and the reactivation of Varicella-zoster virus (VZV) is a potential causal factor for multiple clinical traits. A phenome-wide MR study of anti-VZV immunoglobulin G (IgG) levels with 1370 clinical traits is performed using the UK Biobank cohort, by using instrumental variables (IVs) inside (IVmhc) and outside (IVno.mhc) the MHC region and all together (IVfull). Evidence (FDR<0.05) for a causal effect of anti-VZV IgG levels was found on 22 traits using IVmhc, while no evidence was found when using IVno.mhc or IVfull. MR results between IVmhc and IVno.mhc were noticeably different, as causal associations were in opposite directions between anti-VZV IgG and ten traits. Taken together, the MHC region might have a substantial impact on MR, and therefore, could be potentially considered in future studies.
