Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Salem Rany M, Todd Jennifer N, Sandholm Niina, Cole Joanne B, Chen Wei-Min, Andrews Darrell, Pezzolesi Marcus G, McKeigue Paul M, Hiraki Linda T, Qiu Chengxiang, Nair Viji, Di Liao Chen, Cao Jing Jing, Valo Erkka, Onengut-Gumuscu Suna, Smiles Adam M, McGurnaghan Stuart J, Haukka Jani K, Harjutsalo Valma, Brennan Eoin P, van Zuydam Natalie, Ahlqvist Emma, Doyle Ross, Ahluwalia Tarunveer S, Lajer Maria, Hughes Maria F, Park Jihwan, Skupien Jan, Spiliopoulou Athina, Liu Andrew, Menon Rajasree, Boustany-Kari Carine M, Kang Hyun M, Nelson Robert G, Klein Ronald, Klein Barbara E, Lee Kristine E, Gao Xiaoyu, Mauer Michael, Maestroni Silvia, Caramori Maria Luiza, de Boer Ian H, Miller Rachel G, Guo Jingchuan, Boright Andrew P, Tregouet David, Gyorgy Beata, Snell-Bergeon Janet K, Maahs David M, Bull Shelley B, Canty Angelo J, Palmer Colin N A, Stechemesser Lars, Paulweber Bernhard, Weitgasser Raimund, Sokolovska Jelizaveta, Rovīte Vita, Pīrāgs Valdis, Prakapiene Edita, Radzeviciene Lina, Verkauskiene Rasa, Panduru Nicolae Mircea, Groop Leif C, McCarthy Mark I, Gu Harvest F, Möllsten Anna, Falhammar Henrik, Brismar Kerstin, Martin Finian, Rossing Peter, Costacou Tina, Zerbini Gianpaolo, Marre Michel, Hadjadj Samy, McKnight Amy J, Forsblom Carol, McKay Gareth, Godson Catherine, Maxwell A Peter, Kretzler Matthias, Susztak Katalin, Colhoun Helen M, Krolewski Andrzej, Paterson Andrew D, Groop Per-Henrik, Rich Stephen S, Hirschhorn Joel N, Florez Jose C, SUMMIT Consortium, DCCT/EDIC Research Group, GENIE Consortium
Аннотация
METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.
RESULTS: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1).
CONCLUSIONS: The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.