Pulse lineResearch With Heart Logo

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.

TitleDifferential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.
Publication TypeJournal Article
Year of Publication2022
AuthorsWinkler TW, Rasheed H, Teumer A, et al.
Corporate AuthorsLifeLines Cohort Study, DiscovEHR/MyCode study, VA Million Veteran Program
JournalCommun Biol
Date Published2022 06 13
KeywordsCreatinine, Diabetes Mellitus, Diabetic Nephropathies, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n = 178,691, n = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.

Alternate JournalCommun Biol
PubMed ID35697829
PubMed Central IDPMC9192715
Grant ListI01 CX001897 / CX / CSRD VA / United States
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States