Chronic kidney disease is a growing burden, yet the genetic architecture of kidney function requires further investigation. We performed a genome-wide association study of estimated glomerular filtration rate in 72,298 Korean individuals using a population-specific Korean Biobank Array and genetic imputation with a population matching imputation panel enabling high-resolution variant detection. We identified 30 independent signals including an East Asian-specific rare variant rs535291258. Through fine-mapping and functional annotation using epigenomic data, rs9895661 was predicted to modulate the binding affinity of the transcription factor TBX5, thereby influencing TBX2 expression. We also experimentally validated the allele-specific enhancer activity of this variant. Our results reveal both common and rare variants underlying kidney function in an East Asian population, highlight the value of population-specific approaches and illustrate how integrating epigenomic profiling and experimental approaches with GWAS results can connect genetic associations with molecular mechanisms of kidney function.
Jang et al. (Tue,) studied this question.