Gary Leggatt

Another nice example by @garg1.bsky.social of “dual genetic architecture” of particular genes (Mendelian “causal” and polygenic “risk” alleles) as they relate to kidney diseases and traits #kidneyomics

A Role for Genetic Modifiers in Tubulointerstitial Kidney Diseases With the increased availability of genomic sequencing technologies, the molecular bases for kidney diseases such as nephronophthisis and mitochondrially inherited and autosomal-dominant tubulointersti...

pmc.ncbi.nlm.nih.gov/articles/PMC...

At these sorts of allele frequencies they must co-exist with monogenic conditions in the same gene. It is hard to imagine that they don't have a disease modifying effect, especially when the common variant influences gene expression.

In one association study using UK biobank data nearly every variant in IQCB1 (NPHP5) was found to be significantly associated with urea/creatinine level, it is also a monogenic cause of nephronophthisis (and retinitis pigmentosa) (PMID: 33636100)

And more...MUC1 in ADTKD-MUC1 , but also a very common variant with an allele frequency of 42% (gnomAD genomes),(rs4072037) influences gene expression through alternative splice-site mechanisms and is associated with declining kidney function in GWAS (PMID: 30467309).

It would be great if you could add me thank you