Kidney disease genetic risk variants alter lysosomal beta-mannosidase (<i>MANBA</i>) expression and disease severity.

ABSTRACT: More than 800 million people in the world suffer from chronic kidney disease (CKD). Genome-wide association studies (GWAS) have identified hundreds of loci where genetic variants are associated with kidney function; however, causal genes and pathways for CKD remain unknown. Here, we performed integration of kidney function GWAS and human kidney-specific expression quantitative trait analysis and identified that the expression of beta-mannosidase (MANBA) was lower in kidneys of subjects with CKD risk genotype. We also show an increased incidence of renal failure in subjects with rare heterozygous loss-of-function coding variants in MANBA using phenome-wide association analysis of 40,963 subjects with exome sequencing data. MANBA is a lysosomal gene highly expressed in k

SUBMITTER: Gu X 

PROVIDER: S-EPMC8627675 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature