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

Finnish Diabetic Nephropathy Study (FinnDiane)

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

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 3 10 28 ) 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.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind67
Udgave nummer7
Sider (fra-til)1414-1427
ISSN0046-0192
DOI
StatusUdgivet - 1. jul. 2018

Fingeraftryk

Genome-Wide Association Study
Diabetic Nephropathies
Type 2 Diabetes Mellitus
Glomerular Filtration Rate
Sample Size

Citer dette

Finnish Diabetic Nephropathy Study (FinnDiane). / A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. I: Diabetes. 2018 ; Bind 67, Nr. 7. s. 1414-1427.
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title = "A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes",
abstract = "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 3 10 28 ) 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.",
author = "{van Zuydam}, {Natalie R} and Emma Ahlqvist and Niina Sandholm and Harshal Deshmukh and Rayner, {N William} and Moustafa Abdalla and Claes Ladenvall and Daniel Ziemek and Eric Fauman and Robertson, {Neil R} and McKeigue, {Paul M} and Erkka Valo and Carol Forsblom and Valma Harjutsalo and Annalisa Perna and Erica Rurali and Marcovecchio, {M Loredana} and Igo, {Robert P} and Salem, {Rany M} and Norberto Perico and Maria Lajer and Annemari K{\"a}r{\"a}j{\"a}m{\"a}ki and Minako Imamura and Michiaki Kubo and Atsushi Takahashi and Xueling Sim and Jianjun Liu and {van Dam}, {Rob M} and Guozhi Jiang and Tam, {Claudia H T} and Luk, {Andrea O Y} and Lee, {Heung Man} and Lim, {Cadmon K P} and Szeto, {Cheuk Chun} and So, {Wing Yee} and Chan, {Juliana C N} and Ang, {Su Fen} and Rajkumar Dorajoo and Ling Wang and Clara, {Tan Si Hua} and Amy-Jayne McKnight and Seamus Duffy and Pezzolesi, {Marcus G} and Michel Marre and Beata Gyorgy and Samy Hadjadj and Hiraki, {Linda T} and Cramer Christensen and Ivan Brandslund and Torben Hansen and {Finnish Diabetic Nephropathy Study (FinnDiane)}",
note = "{\circledC} 2018 by the American Diabetes Association.",
year = "2018",
month = "7",
day = "1",
doi = "10.2337/db17-0914",
language = "English",
volume = "67",
pages = "1414--1427",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "7",

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Finnish Diabetic Nephropathy Study (FinnDiane) 2018, 'A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes', Diabetes, bind 67, nr. 7, s. 1414-1427. https://doi.org/10.2337/db17-0914

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes. / Finnish Diabetic Nephropathy Study (FinnDiane).

I: Diabetes, Bind 67, Nr. 7, 01.07.2018, s. 1414-1427.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Sandholm, Niina

AU - Deshmukh, Harshal

AU - Rayner, N William

AU - Abdalla, Moustafa

AU - Ladenvall, Claes

AU - Ziemek, Daniel

AU - Fauman, Eric

AU - Robertson, Neil R

AU - McKeigue, Paul M

AU - Valo, Erkka

AU - Forsblom, Carol

AU - Harjutsalo, Valma

AU - Perna, Annalisa

AU - Rurali, Erica

AU - Marcovecchio, M Loredana

AU - Igo, Robert P

AU - Salem, Rany M

AU - Perico, Norberto

AU - Lajer, Maria

AU - Käräjämäki, Annemari

AU - Imamura, Minako

AU - Kubo, Michiaki

AU - Takahashi, Atsushi

AU - Sim, Xueling

AU - Liu, Jianjun

AU - van Dam, Rob M

AU - Jiang, Guozhi

AU - Tam, Claudia H T

AU - Luk, Andrea O Y

AU - Lee, Heung Man

AU - Lim, Cadmon K P

AU - Szeto, Cheuk Chun

AU - So, Wing Yee

AU - Chan, Juliana C N

AU - Ang, Su Fen

AU - Dorajoo, Rajkumar

AU - Wang, Ling

AU - Clara, Tan Si Hua

AU - McKnight, Amy-Jayne

AU - Duffy, Seamus

AU - Pezzolesi, Marcus G

AU - Marre, Michel

AU - Gyorgy, Beata

AU - Hadjadj, Samy

AU - Hiraki, Linda T

AU - Christensen, Cramer

AU - Brandslund, Ivan

AU - Hansen, Torben

AU - Finnish Diabetic Nephropathy Study (FinnDiane)

N1 - © 2018 by the American Diabetes Association.

PY - 2018/7/1

Y1 - 2018/7/1

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 3 10 28 ) 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 3 10 28 ) 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.

U2 - 10.2337/db17-0914

DO - 10.2337/db17-0914

M3 - Journal article

VL - 67

SP - 1414

EP - 1427

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 7

ER -