Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom

Abstract Objectives This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people in the United Kingdom as they are an understudied genetic ancestry group with disproportionate disease burden. Methods Five genes ( ABCB4, ABCB11, ATP8B1, NR1H4, TJP2 ) were interrogated by low/mid whole exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency <5%. Variants were filtered and annotated. Rare variant burden analysis was conducted. Variants associated with a phenotype or predicted to be likely pathogenic (LP) underwent protein structure and modelling analysis in silico. Results Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and…