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Reference: Sandholm, N, Van Zuydam, N, Ahlqvist, E et al., (2016). The genetic landscape of renal complications in type 1 diabetes. Journal of the American Society of Nephrology, 28 (2).Citable link to this page:

 

The genetic landscape of renal complications in type 1 diabetes.

Abstract: Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2016-07-17 Funder: Seventh Framework Programme   Funder: Innovative Medicine Initiative   Notes:Copyright © 2017 by the American Society of Nephrology

Bibliographic Details

Publisher: American Society for Nephrology

Publisher Website: http://www.asnjournals.org/

Journal: Journal of the American Society of Nephrologysee more from them

Publication Website: http://jasn.asnjournals.org/

Volume: 28

Issue: 2

Extent: 557-574

Issue Date: 2016-09Identifiers

Doi: https://doi.org/10.1681/ASN.2016020231

Issn: 1533-3450

Issn: 1046-6673

Uuid: uuid:7b6e8ff1-34e2-43a4-bcb8-3734fd36e010

Urn: uri:7b6e8ff1-34e2-43a4-bcb8-3734fd36e010

Pubs-id: pubs:645829 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: FinnDiane Study Group DCCT/EDIC Study Group GENIE Consortium SUMMIT Consortium

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Autor: Sandholm, N - - - Van Zuydam, N - Oxford, MSD, RDM, RDM OCDEM - - - Ahlqvist, E - - - Juliusdottir, T - - - Deshmukh, HA - - - Ra

Fuente: https://ora.ox.ac.uk/objects/uuid:7b6e8ff1-34e2-43a4-bcb8-3734fd36e010



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