A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

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A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. / van Zuydam, Natalie R; Ahlqvist, Emma; Ladenvall, Claes; Almgren, Peter; Schulz, Christina-Alexandra; Orho-Melander, Marju; Melander, Olle; Lyssenko, Valeriya; Tuomi, Tiinamaija; Groop, Leif C; McCarthy, Mark I; Finnish Diabetic Nephropathy Study (FinnDiane); Hong Kong Diabetes Registry Theme-based Research Scheme Project Group; GENIE (Genetics of Nepropathy an International Effort) Consortium; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group; SUMMIT Consortium ; Kravic, Jasmina (Contributor).

In: Diabetes, Vol. 67, No. 7, 07.2018, p. 1414-1427.

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van Zuydam, NR, Ahlqvist, E, Ladenvall, C, Almgren, P, Schulz, C-A, Orho-Melander, M, Melander, O, Lyssenko, V, Tuomi, T, Groop, LC, McCarthy, MI, Finnish Diabetic Nephropathy Study (FinnDiane), Hong Kong Diabetes Registry Theme-based Research Scheme Project Group, GENIE (Genetics of Nepropathy an International Effort) Consortium, Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, SUMMIT Consortium & Kravic, J 2018, 'A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes', Diabetes, vol. 67, no. 7, pp. 1414-1427. https://doi.org/10.2337/db17-0914

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van Zuydam NR, Ahlqvist E, Ladenvall C, Almgren P, Schulz C-A, Orho-Melander M, Melander O, Lyssenko V, Tuomi T, Groop LC, McCarthy MI, Finnish Diabetic Nephropathy Study (FinnDiane), Hong Kong Diabetes Registry Theme-based Research Scheme Project Group, GENIE (Genetics of Nepropathy an International Effort) Consortium, Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, SUMMIT Consortium, Kravic J. 2018. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. Diabetes. 67(7):1414-1427. https://doi.org/10.2337/db17-0914

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van Zuydam, Natalie R ; Ahlqvist, Emma ; Ladenvall, Claes ; Almgren, Peter ; Schulz, Christina-Alexandra ; Orho-Melander, Marju ; Melander, Olle ; Lyssenko, Valeriya ; Tuomi, Tiinamaija ; Groop, Leif C ; McCarthy, Mark I ; Finnish Diabetic Nephropathy Study (FinnDiane) ; Hong Kong Diabetes Registry Theme-based Research Scheme Project Group ; GENIE (Genetics of Nepropathy an International Effort) Consortium ; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group ; SUMMIT Consortium ; Kravic, Jasmina. / A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. In: Diabetes. 2018 ; Vol. 67, No. 7. pp. 1414-1427.

RIS

TY - JOUR

T1 - A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

AU - van Zuydam, Natalie R

AU - Ahlqvist, Emma

AU - Ladenvall, Claes

AU - Almgren, Peter

AU - Schulz, Christina-Alexandra

AU - Orho-Melander, Marju

AU - Melander, Olle

AU - Lyssenko, Valeriya

AU - Tuomi, Tiinamaija

AU - Groop, Leif C

AU - McCarthy, Mark I

AU - Finnish Diabetic Nephropathy Study (FinnDiane)

AU - Hong Kong Diabetes Registry Theme-based Research Scheme Project Group

AU - GENIE (Genetics of Nepropathy an International Effort) Consortium

AU - Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group

AU - SUMMIT Consortium

A2 - Kravic, Jasmina

N1 - © 2018 by the American Diabetes Association.

PY - 2018/7

Y1 - 2018/7

N2 - Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.

AB - Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2/complications

KW - Diabetic Nephropathies/epidemiology

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Kidney Failure, Chronic/complications

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Renal Insufficiency, Chronic/complications

U2 - 10.2337/db17-0914

DO - 10.2337/db17-0914

M3 - Article

VL - 67

SP - 1414

EP - 1427

JO - Diabetes

T2 - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 7

ER -