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Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-09861-z

2041-1723

Sarah E. Graham, Jonas B. Nielsen, Matthew Zawistowski, Wei Zhou, Lars G. Fritsche, Maiken E. Gabrielsen, Anne Heidi Skogholt, Ida Surakka, Whitney Hornsby, Damian Fermin, Daniel B. Larach, Sachin Kheterpal, Chad M. Brummett, Seunggeun Lee, Hyun Min Kang, Gonçalo R. Abecasis, Solfrid Romundstad, Stein Hallan, Matthew G. Sampson, Kristian Hveem, Cristen J. Willer,

Genetic Associations and Epidemiology

Abstract Chronic kidney disease (CKD) is a growing health burden currently affecting 10–15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analysis results, we show that associated variants are generally predictive of CKD with only modest improvements in detection compared with other known clinical risk factors. Collectively, these results yield additional insight into the genetic factors underlying kidney function and progression to CKD.