Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).
СтатьяМетаанализПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Iyengar Sudha K, Sedor John R, Freedman Barry I, Kao W H Linda, Kretzler Matthias, Keller Benjamin J, Abboud Hanna E, Adler Sharon G, Best Lyle G, Bowden Donald W, Burlock Allison, Chen Yii-Der Ida, Cole Shelley A, Comeau Mary E, Curtis Jeffrey M, Divers Jasmin, Drechsler Christiane, Duggirala Ravi, Elston Robert C, Guo Xiuqing, Huang Huateng, Hoffmann Michael Marcus, Howard Barbara V, Ipp Eli, Kimmel Paul L, Klag Michael J, Knowler William C, Kohn Orly F, Leak Tennille S, Leehey David J, Li Man, Malhotra Alka, März Winfried, Nair Viji, Nelson Robert G, Nicholas Susanne B, O'Brien Stephen J, Pahl Madeleine V, Parekh Rulan S, Pezzolesi Marcus G, Rasooly Rebekah S, Rotimi Charles N, Rotter Jerome I, Schelling Jeffrey R, Seldin Michael F, Shah Vallabh O, Smiles Adam M, Smith Michael W, Taylor Kent D, Thameem Farook, Thornley-Brown Denyse P, Truitt Barbara J, Wanner Christoph, Weil E Jennifer, Winkler Cheryl A, Zager Philip G, Igo Robert P, Hanson Robert L, Langefeld Carl D, Family Investigation of Nephropathy and Diabetes (FIND)
Аннотация
Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.