rs10862375 - PPFIA2 - LINC02426

Magnitude 4.5 · 2 studies on file

Reported associations

• Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function. - Nature genetics (2024) · Loeb GB, Kathail P, Shuai RW, Chung R, Grona RJ, Peddada S, Sevim V, Federman S, Mader K, Chu AY, Davitte J, Du J, Gupta AR, Ye CJ, Shafer S, Przybyla L, Rapiteanu R, Ioannidis NM, Reiter JF · PubMed 39256582

  Kidney failure, the decrease of kidney function below a threshold necessary to support life, is a major cause of morbidity and mortality. We performed a genome-wide association study (GWAS) of 406,504 individuals in the UK Biobank, identifying 430 loci affecting kidney function in middle-aged adults. To investigate the cell types affected by these loci, we integrated the GWAS with human kidney candidate cis-regulatory elements (cCREs) identified using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). Overall, 56% of kidney function heritability localized to kidney tubule epithelial cCREs and an additional 7% to kidney podocyte cCREs. Thus, most heritable differences in adult kidney function are a result of altered gene expression in these two cell types. Using

• Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease. - Nature genetics (2022) · Liu H, Doke T, Guo D, Sheng X, Ma Z, Park J, Vy HMT, Nadkarni GN, Abedini A, Miao Z, Palmer M, Voight BF, Li H, Brown CD, Ritchie MD, Shu Y, Susztak K · PubMed 35710981

  More than 800 million people suffer from kidney disease, yet the mechanism of kidney dysfunction is poorly understood. In the present study, we define the genetic association with kidney function in 1.5 million individuals and identify 878 (126 new) loci. We map the genotype effect on the methylome in 443 kidneys, transcriptome in 686 samples and single-cell open chromatin in 57,229 kidney cells. Heritability analysis reveals that methylation variation explains a larger fraction of heritability than gene expression. We present a multi-stage prioritization strategy and prioritize target genes for 87% of kidney function loci. We highlight key roles of proximal tubules and metabolism in kidney function regulation. Furthermore, the causal role of SLC47A1 in kidney disease is defined in mice wi

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