Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
received:
22
09
2018
accepted:
03
04
2019
entrez:
25
4
2019
pubmed:
25
4
2019
medline:
14
6
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31015462
doi: 10.1038/s41467-019-09861-z
pii: 10.1038/s41467-019-09861-z
pmc: PMC6478837
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1847Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK108805
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127564
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135824
Pays : United States
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