Kidney disease genetic risk variants alter lysosomal beta-mannosidase (MANBA) expression and disease severity https://stm.sciencemag.org/content/13/576/eaaz1458
The study is lead by @Xiangchen_Gu @XinSheng7 and Holly Yang. Kidney function GWAS identified hundreds of variants associated with kidney function, but causal genes, cell types and mechanisms encoded remains unknown
We took a closer look chr4. Coloc integration of the common GWAS variants and eQTL studies showed that MANBA (lysosomal beta mannosidase) is the likely causal gene. Furthermore kidney disease incidence was higher in subjects with rare loss of function coding variants
MANBA deficiency causes structural and functional lysosomal changes, a block in autophagy and endocytosis defect in kidney proximal tubules
These results illustrate the convergence of common noncoding and rare coding variants in MANBA in kidney disease development and demonstrate the role of the endolysosomal system in kidney disease development.
Thank you for the coauthors BioMe @ckumardeep @ErwinBottinger @girish_nadkarni @Regeneron genetics center, PMBB @MarylynRitchie @danrader333 @JoeInGenes @RachelKember @damrauer @yian_kia @jihwan_park724 @CX_quorly @podocytes and many more !