Causal Genetic Inference Using Haplotypes as Instrumental Variables

In this study, we propose to replace SNPs with haplotypes as IVs to increase the variant‐expression association and thus improve the casual effect inference of the expression. In the classical two‐stage procedure, we developed a haplotype regression model combined with a model selection procedure to identify optimal instruments. The performance of the new method was evaluated through simulations and compared with the IV approaches using observed multiple SNPs. Our results showed the gain of power to detect a causal effect of gene or protein on the outcome using haplotypes compared with using only observed SNPs, under either complete or missing genotype scenarios. We applied our proposed method to a study of the effect of interleukin‐1 beta (IL‐1β) protein expression on the 90‐day survival following sepsis and found that overly expressed IL‐1β is likely to increase mortality.

Source: Genetic Epidemiology - December 1, 2015 Category: Epidemiology Authors: Fan Wang, Nuala J. Meyer, Keith R. Walley, James A. Russell, Rui Feng Tags: Research Article Source Type: research