Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis
Graham, Sarah E.; Nielsen, Jonas B.; Zawistowski, Matthew; Zhou, Wei; Fritsche, Lars G.; Gabrielsen, Maiken Elvestad; Skogholt, Anne Heidi; Surakka, Ida; Hornsby, Whitney E.; Fermin, Damian; Larach, Daniel B.; Kheterpal, Sachin; Brummett, Chad M.; Lee, Seunggeun; Kang, Hyun Min; Abecasis, Goncalo; Romundstad, Solfrid; Hallan, Stein; Sampson, Matthew G.; Hveem, Kristian; Willer, Cristen J.
Journal article, Peer reviewed
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Date
2019Metadata
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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.