GWAS of Hematuria

Area of Science:

• Genetics
• Nephrology
• Genomics

Background:

• Glomerular hematuria can stem from various causes, with genetic factors like Alport syndrome and IgA nephropathy playing a role.
• Identifying genetic variants associated with hematuria is crucial for understanding its pathogenesis and developing targeted therapies.

Purpose of the Study:

• To identify genetic variants linked to hematuria in a large cohort.
• To investigate the genetic architecture of glomerular hematuria and discover novel associated loci.

Main Methods:

• Utilized summary statistics from the UK Biobank, focusing on White British participants.
• Employed conditional analysis to identify independent genetic signals at the COL4A4-COL4A3 and HLA loci.
• Reimputed genetic data using the Trans-Omics for Precision Medicine Program.

Main Results:

• Six loci (PDPN, COL4A4-COL4A3, HLA-B, SORL1, PLLP, and TGFB1) met genome-wide significance for association with hematuria.
• A significant association was found with COL4A4 p.Ser969X and independent variants in COL4A3 and COL4A4.
• The HLA-B*0801 haplotype showed a strong association with hematuria.

Conclusions:

• The study successfully identified six genetic loci associated with hematuria.
• Independent variants within the COL4A4-COL4A3 locus and the HLA-B gene were confirmed.
• Three novel loci, including an intronic variant in PDPN, were reported, highlighting new genetic factors in hematuria.