Host genetic factors underlying the link between the microbiome and rheumatoid arthritis

Abstract

There is mounting interest in the commensal microbiota as a factor in the aetiology of rheumatoid arthritis (RA). The potential influence of host genetic factors has been little explored. In this thesis, I investigate the link between the microbiome and RA, with particular regard to the influence of host genetic factors.
I begin by synthesising and reviewing prior relevant literature. I next consider appropriate methods for analysis of the microbiome. I consider in particular detail, the method for pre-processing the raw sequencing data, which is influential for the resolution of all further analyses in this thesis. I use polygenic risk scoring to capture participants’ genetic risk of RA. I take a novel approach of exploring microbiota association with genetic risk of RA in unaffected participants, and juxtapose this by investigating the difference in the microbiota between RA discordant twins, thereby focussing on genetic association in the first approach and controlling for genetic factors in the second.

Date of Award	2021
Original language	English
Awarding Institution	King's College London
Supervisor	Claire Steves (Supervisor) & Frances Williams (Supervisor)