Expressive

rs11135916 - EBF2 - RNA5SP258

Magnitude 2.2 · 5 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

  • Genetics of 35 blood and urine biomarkers in the UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 33462484

    ABSTRACT: Clinical laboratory tests are a critical component of the continuum of care. We evaluate the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank (n=363,228 individuals). We identify 1,857 loci associated with at least one trait, containing 3,374 fine-mapped associations, and additional sets of large-effect (> 0.1 sd) protein-altering, HLA, and copy-number variant associations. Through Mendelian Randomization analysis, we discover 51 causal relationships, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, we develop polygenic risk scores for each biomarker and built 'multi-PRS' models for diseases using 35 PRSs simultaneously, which improved chronic kidney disease, type 2 diabetes, gout, and alcoholic cirr

  • Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures - Unknown journal (n.d.) · Unknown authors · PubMed 40436827

    ABSTRACT: Genome-wide association studies (GWAS) have predominantly focused on European ancestry populations, limiting biological discoveries across diverse populations. Here we report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 301 previously unreported genetic loci in KCPS2, including an association between thyroid-stimulating hormone and CD36. Meta-analysis with the Korean Genome and Epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 4588 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotrop

  • Genetic analysis of elevated levels of creatinine and cystatin C biomarkers reveals novel genetic loci associated with kidney function - Unknown journal (n.d.) · Unknown authors · PubMed 39927731

    ABSTRACT: Abstract The rising prevalence of chronic kidney disease (CKD), affecting an estimated 37 million adults in the United States, presents a significant global health challenge. CKD is typically assessed using estimated Glomerular Filtration Rate (eGFR), which incorporates serum levels of biomarkers such as creatinine and cystatin C. However, these biomarkers do not directly measure kidney function; their elevation in CKD results from diminished glomerular filtration. Genome-wide association studies (GWAS) based on eGFR formulas using creatinine (eGFRcre) or cystatin C (eGFRcys) have identified distinct non-overlapping loci, raising questions about whether these loci govern kidney function or biomarker metabolism. In this study, we show that GWAS on creatinine and cystatin C levels

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