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Gary Leggatt

@garg1.bsky.social

500 followers 381 following 5 posts

Consultant Nephrologist, Sussex Kidney Unit, UK Genetic Kidney Diseases, Kidney Stones

Posts Replies Media

Reposted by Gary Leggatt

Matt Sampson @kidneyomicsamps.bsky.social · 16/11/2024

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

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Gary Leggatt @garg1.bsky.social · 16/11/2024

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

pmc.ncbi.nlm.nih.gov

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...

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Gary Leggatt @garg1.bsky.social · 16/11/2024

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.

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Gary Leggatt @garg1.bsky.social · 16/11/2024

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)

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Gary Leggatt @garg1.bsky.social · 16/11/2024

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).

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Gary Leggatt @garg1.bsky.social · 16/11/2024

It would be great if you could add me thank you

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