Genome-Wide Association Study of Quantitative Kidney Function in 52,531 Individuals with Diabetes Identifies Five Diabetes-Specific Loci

作者：Joanne B. Cole, Emma H. Dahlström, Damian Fermin, Yogesh Gupta, Claire Hill, Laura J. Smyth, Hongbo Liu, Raymond J. Kreienkamp, Marcus G. Pezzolesi, Jingjing Cao, Erkka Valo, Wei‐Min Chen, Suna Önengüt-Gümüşcü, Stephen S. Rich, Eoin Brennan, Darrell Andrews, Ciarán Kennedy, Harvest F. Gu, Lars Stechemesser, Raimund Weitgasser, Jeļizaveta Sokolovska, Lina Radzevičienė, Rasa Verkauskienė, Nicolae Mircea Panduru, Peter Rossing, Tarunveer S. Ahluwalia, Gianpaolo Zerbini, Michel Marre, Samy Hadjadj, Tina Costacou, Rachel G. Miller, Ronald Klein, Kristine E. Lee, Janet K. Snell‐Bergeon, Maria Luiza Caramori, Michael Mauer, Kerstin Brismar, Petter Bjornstad, Amy Jayne McKnight, Gareth J. McKay, Viji Nair, Rany M. Salem, Per‐Henrik Groop, Catherine Godson, Katalin Suszták, Matthias Kretzler, Alexander P. Maxwell, Andrzej S. Królewski, Andrew D. Paterson, Niina Sandholm, José C. Florez, Joel N. Hirschhorn · 发表于：Journal of the American Society of Nephrology · 年份：2025 · DOI：10.1681/asn.0000000718 · 被引用次数：6 · 研究领域：Birth, Development, and Health、Epigenetics and DNA Methylation、Genetic Associations and Epidemiology

Key Points Comprehensive genome-wide association study of eGFR in diabetes, accounting for diabetes duration, kidney disease, and known modifiers, identified novel genetic effects. Incorporation of various kidney multi-omics data provides supporting evidence for the role of novel genome-wide association study loci in diabetic kidney disease. Background Diabetic kidney disease (DKD) is a serious diabetes complication caused by both environmental and genetic risk factors. Previous genome-wide association studies (GWAS) have identified several loci associated with kidney function and kidney disease in the general population and, to a lesser extent, in diabetes. Methods To uncover the genetic factors driving diabetes-induced kidney function, we conducted a series of GWAS meta-analyses of eGFR in 17,267 individuals with type 1 diabetes and 35,264 with type 2 diabetes (52,531 total), using multiple well-characterized cohorts of type 1 diabetes DKD and data from the UK Biobank and SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools (SUMMIT) consortium. We further accounted for DKD case/control status, diabetes duration and subtype, body mass index, glycated hemoglobin levels, and the relationship between eGFR and albuminuria. Results GWAS identified 13 loci associated with eGFR ( P < 5×10 −8 ), with five loci (candidate genes: HIPK3 , TRIM5 , RORA , ERBB4 , and BCL6 / LPP ) not associated with or were in opposite directions as compared wit...