Open AccessA Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
Author(s) -
Natalie R. van Zuydam,
Emma Ahlqvist,
Niina Sandholm,
Harshal Deshmukh,
Nigel W. Rayner,
Moustafa Abdalla,
Claes Ladenvall,
Daniel Ziemek,
Eric B. Fauman,
Neil R. Robertson,
Paul McKeigue,
Erkka Valo,
Carol Forsblom,
Valma Harjutsalo,
Annalisa Perna,
Erica Rurali,
M. Loredana Marcovecchio,
Robert P. Igo,
Rany M. Salem,
Norberto Perico,
Maria Lajer,
Annemari Käräjämäki,
Minako Imamura,
Michiaki Kubo,
Atsushi Takahashi,
Xueling Sim,
Jianjun Liu,
Rob M. van Dam,
Guozhi Jiang,
Claudia H.T. Tam,
Andrea O. Y. Luk,
Heung Man Lee,
Cadmon K.P. Lim,
CheukChun Szeto,
Wing Yee So,
Juliana C.N. Chan,
Su Fen Ang,
Rajkumar Dorajoo,
Ling Wang,
Tan Si Hua Clara,
Amy Jayne McKnight,
Seamus Duffy,
Marcus G. Pezzolesi,
Michel Marre,
Beata Gyorgy,
Samy Hadjadj,
Linda T. Hiraki,
Tarunveer S. Ahluwalia,
Peter Almgren,
ChristinaAlexandra Schulz,
Marju OrhoMelander,
Allan Linneberg,
Cramer Christensen,
Daniel R. Witte,
Niels Grarup,
Ivan Brandslund,
Olle Melander,
Andrew D. Paterson,
DavidAlexandre Trégouët,
Alexander P. Maxwell,
Su Chi Lim,
Ronald C.W.,
E Shyong Tai,
Shiro Maeda,
Valeriya Lyssenko,
Jaakko Tuomilehto,
Andrzej S. Królewski,
Stephen S. Rich,
Joel N. Hirschhorn,
José C. Florez,
David B. Dunger,
Oluf Pedersen,
Torben Hansen,
Peter Rossing,
Giuseppe Remuzzi,
M. Julia Brosnan,
Nicholette D. Palmer,
PerHenrik Groop,
Helen M. Colhoun,
Leif Groop,
Mark I. McCarthy,
Satu Koivula,
T. Uggeldahl,
Terje Forslund,
A. Halonen,
A. Koistinen,
P. Koskiaho,
M. Laukkanen,
Juha Saltevo,
Miia Tiihonen,
M. Forsen,
Helena Granlund,
A.-C. Jönsson,
B. Nyroos,
Pentti Kinnunen,
A. Orvola,
Tapani Salonen,
A. Vähänen,
Kotka R. Paldanius,
M Riihelä,
L. Ryysy,
Kemi H. Laukkanen,
P. Nyländen,
Anni Sademies,
S. Anderson,
Barbro Asplund,
U. Byskata,
P. Liedes,
M. Kuusela,
T. Virkkala,
Anssi Nikkola,
E. Ritola,
Tapiola M. Niska,
Harri Juhani Saarinen,
Samaria E. Oukko-Ruponen,
Tuula Virtanen,
Viherlaakso A. Lyytinen,
P H Kari,
T. Simonen,
Suutarila A. Kaprio,
Jorma Kärkkäinen,
B. Rantaeskola,
Toolo P. Kääriäinen,
J R Haaga,
A.-L. Pietiläinen,
Sanna Klemetti,
T. Nyandoto,
E. Rontu,
S. Satuli-Autere,
Korso R. Toivonen,
H. Virtanen Lansimaki,
Riitta Ahonen,
M. Ivaska-Suomela,
Anneli Jauhiainen,
Martinlaakso M. Laine,
T. Pellonpää,
R. Puranen,
Myyrmaki A. Airas,
Juha Laakso,
K. Rautavaara,
Rekola M. Erola,
E. Jatkola,
Tikkurila R. Lönnblad,
Anna Malm,
Jyrki Mäkelä,
E. Rautamo,
P. Hentunen,
J. Lagerstam,
Maija Feodoroff,
Daniel Gordin,
Outi Heikkilä,
Kustaa Hietala,
J. Fagerudd,
Minna A. Korolainen,
L. Kyllönen,
Janne Kytö,
S. Lindh,
Kim Pettersson-Fernholm,
Milla RosengårdBärlund,
Amanda Sandelin,
Lena M. Thorn,
Jaana Tuomikangas,
T. Vesisenaho,
Johan Wadén,
V. Sipilä,
Forssa T. Kalliomäki,
J. Koskelainen,
R. Nikkanen,
N. Savolainen,
Hannu Sulonen,
E. Valtonen,
Leeorvio,
Anne Hämäläinen,
E. Toivanen,
Jamsa A. Parta,
I. Pirttiniemi,
S. Aranko,
Satu Ervasti,
Ari Kuusisto,
T. Leppälä,
Katriiikkilä,
L. Pekkonen,
K. Jokelainen,
Kristiina Kananen,
Matti Karjalainen,
Pentti Kemppainen,
A.-M. Mankinen,
A. Reponen,
M. Sankari,
Pauli Suominen,
Anu K. Lappalainen,
Maarit Liimatainen,
J. Santaholma,
Ari Aimolahti,
Elisa Huovinen,
V. Ilkka,
M. Y. Lehtimäki,
E. Pälikkö-Kontinen,
A. Vanhanen,
E. Koskinen,
Timo Siitonen,
Erja Huttunen,
Risto Ikäheimo,
Pauli Karhapää,
Päivi Kekäläinen,
M. Laakso,
Timo A. Lakka,
E Lampainen,
Leena Moilanen,
Sanna Tanskanen,
Leo Niskanen,
U. Tuovinen,
Ilkka Vauhkonen,
Erkki Voutilainen,
Yü Huang,
Hui Y. Lan,
Si Lok,
Brian Tomlinson,
Stephen KwokWing Tsui,
Weichuan Yu,
Kevin Y.L. Yip,
TingFung Chan,
Xiaodan Fan,
Nelson L.S. Tang,
Xiao Yu Tian,
Kei Hang Katie Chan,
Fangying Xie,
Alex C.W. Ng,
Grace P.Y. Cheung,
Ming Wai Yeung,
Mai Shi,
Fei Xie,
Sen Zhang,
Yu Pu,
Meng Weng,
David A. Savage,
James D. Walker,
Stephen Thomas,
Giancarlo Viberti,
A.J.M. Boulton,
S. M. Marshall,
Andrew Demaine,
B. A. Millward,
Steve Baín,
VillePetteri Mäkinen,
Aila J. Ahola,
Emma H. Dahlström,
Markku Lehto,
Raija Lithovius,
Nicolae Mircea Panduru,
Maija Parkkonen,
Markku Saraheimo,
Jenny Söderlund,
Aino SoroPaavonen,
Anna Syreeni,
Nina Tolonen,
Gareth J. McKay,
Tamara Isakova,
Candace Guiducci,
Andrew M. Taylor,
Daniel B. Mirel,
Winfred W. Williams,
Eoin Brennan,
Denise M. Sadlier,
Finian Martin,
Catherine Godson,
Lynne Mayer,
Rose GubitosiKlug,
P. A. Bourne,
Mark H. Schutta,
M. E. Lackaye,
Naina Sinha Gregory,
Davida F. Kruger,
J. Kimberly Jones,
Arti Bhan,
E. Golden,
Lloyd Paul Aiello,
Mary Larkin,
David Nathan,
G. Ziegler,
Susan Caulder,
C. Pittman,
Louis M. Luttrell,
Maria F. LopesVirella,
Mary L. Johnson,
K. Gunyou,
Richard M. Bergenstal,
B. Vittetoe,
William I. Sivitz,
Nancy Flaherty,
John P. Bantle,
Susan Hitt,
David Goldstein,
Dean P. Hainsworth,
Lori Cimino,
Trevor J. Orchard,
Christine Wigley,
Samuel DagogoJack,
Suzanne Strowig,
Philip Raskin,
Annette Barnie,
Bernard Zinman,
Robyn Fahlstrom,
Jerry P. Palmer,
J. Harth,
Marsha Driscoll,
Charlotte McDonald,
Janie Lipps Hagan,
Michael May,
L. Levandoski,
Neil H. White,
P. Gatcomb,
William V. Tamborlane,
Daphne T. Adelman,
Susan Colson,
Mark E. Molitch,
Gayle M. Lorenzi,
Sunder Mudaliar,
S. Johnsonbaugh,
Ryan Miller,
Janene L. Canady,
David S. Schade,
M.L. Bernal,
John I. Malone,
Anthony Morrison,
Catherine Martin,
William H. Herman,
Rodica PopBusui,
Catherine C. Cowie,
Ellen W. Leschek,
Patricia A. Cleary,
John M. Lachin,
B. Zinman,
Barbara H. Braffett,
Mike Steffes,
Valerie Arends,
Barbara Blodi,
Ronald Danis,
Daniel Lawrence,
Hugh Wabers,
Elsayed Z. Soliman,
ZhuMing Zhang,
Charles J. Campbell,
Susan Hensley,
Lisa Keasler,
Mark Michael,
Markus Albertini,
Carine Boustany,
Alexander Ehlgen,
Martin Gerl,
Jochen Huber,
Corinna Schölch,
Heike ZimdahlGelling,
Elisabet Agardh,
Tord Ajanki,
Nibal Al Maghrabi,
Jan Apelqvist,
Eva Bengtsson,
Lisa Berglund,
Harry Björckbacka,
Ulrika Blom-Nilsson,
Mattias Borell,
Agneta Burström,
Corrado Cilio,
Magnus Cinthio,
Karl Dreja,
Pontus Dunér,
Daniel Engelbertsen,
João Fadista,
Marı́a Gómez,
Isabel Gonçalves,
Bo Hedblad,
Anna Hultgårdh,
Martin E. Johansson,
Cecilia Kennbäck,
Jasmina Kravić,
Åke Lernmark,
Eero Lindholm,
Charlotte Ling,
Holger Luthman,
Malin Neptin,
Jan Nilsson,
Peter M. Nilsson,
Tobias Nilsson,
Gunilla Nordin,
Emilia Ottoson-Laakso,
Annie Persson,
Margaretha Persson,
Mats-Åke Persson,
Jacqueline Postma,
Elisabeth Pranter,
Sara Rattik,
Gunnar Sterner,
Lilian Tindberg,
Maria Wigren,
Anna V. Zetterqvist,
Mikael Åkerlund,
Gerd Östling,
Timo Kanninen,
Anni Ahonen-Bishopp,
Anita Eliasson,
Timo Herrala,
Päivi Tikka-Kleemola,
Anders Hamsten,
Christer Betsholtz,
A. Björkholm,
Fariba Foroogh,
Guillem Genové,
Karl Gertow,
Bruna Gigante,
Bing He,
Karin Leander,
Olga McLeod,
Maria Nastase-Mannila,
Jaako Patrakka,
Angela Silveira,
Rona J. Strawbridge,
Karl Tryggvason,
Max Vikström,
John Öhrvik,
AnneMay Österholm,
Barbara Thorand,
Christian Gieger,
Harald Grallert,
Tonia Ludwig,
Barbara Nitz,
Andrea L.C. Schneider,
Rui WangSattler,
Astrid Zierer,
Ariela Benigni,
Roberta Donadelli,
Mariadomenica Lesti,
Marioris,
Rossella Piras,
Piero Ruggenenti,
Ludo Chassin,
Neil Dalton,
John Deanfield,
Jane Horsford,
Clare Rice,
James H.F. Rudd,
Neil Walker,
Karen Whitehead,
Max Wong,
F. Dennette Adams,
Tahira Akbar,
J. J. F. Belch,
Fiona Dove,
A Ellingford,
Bassam Farran,
Mike Ferguson,
Gary L. Henderson,
J. Graeme Houston,
Faisel Khan,
Graham Leese,
Yiyuan Liu,
Shona Livingstone,
Helen C. Looker,
Margaret McCann,
Stuart J. McGurnaghan,
Andrew D. Morris,
D. J. Newton,
Ewan R. Pearson,
G Reekie,
Natalie Smith,
Angela C. Shore,
Kuni Aizawa,
Claire Ball,
Nick G. Bellenger,
Francesco Casanova,
Timothy M. Frayling,
Phil Gates,
Kim M. Gooding,
Andrew T. Hattersley,
R Ling,
David M. Mawson,
Robin Shandas,
W. David Strain,
Clare E. Thorn,
Ulf Smith,
Ann Hammarstedt,
Hans Häring,
Georgio Sesti,
Emma Fagerholm,
Maikki Parkkonen,
Iiro Toppila,
Veikko Salomaa,
Aki S. Havulinna,
Kati Kristiansson,
Pia Okamo,
Tomi Peltola,
Markus Perola,
Arto Pietilä,
Samuli Ripatti,
Marketta Taimi,
Seppo YläHerttuala,
Mohan Babu,
Marike H. Dijkstra,
Erika Gurzeler,
Jenni Huusko,
Ivana Kholová,
Markku Laakso,
Mari Merentie,
Marja Poikolainen,
Mark McCarthy,
Chris Groves,
Thorhildur Juliusdottir,
Fredrik Karpe,
Vasiliki Lagou,
Will Rayner,
Neil Robertson,
Claudio Cobelli,
Barbara Di Camillo,
Francesca Finotello,
Francesco Sambo,
Gianna Toffolo,
Emanuele Trifoglio,
Riccardo Bellazzi,
Nicola Barbarini,
Mauro Bucalo,
Christiana Larizza,
Paolo Magni,
Alberto Malovini,
Simone Marini,
Francesca Mulas,
Silvana Quaglini,
Lucia Sacchi,
Francesca Vitali,
Ele Ferrannini,
Beatrice Boldrini,
M. Kozàkovà,
Andrea Mari,
C. Morizzo,
L.G.S. Mota,
Andrea Natali,
Carlo Palombo,
Elena Venturi,
Mark S. Walker,
Carlo Patrono,
Francesca Pagliaccia,
Bianca Rocca,
Pirjo Nuutila,
Johanna Haukkala,
Juhani Knuuti,
Anne Roivainen,
Antti Saraste,
Paul McKeague,
Marco Colombo,
Birgit Steckel-Hamann,
Krister Bokvist,
Sudha Shankar,
Mélissa Thomas,
LiMing Gan,
Suvi E. Hein,
AnnCathrine JönssonRylander,
Remi A. Momo,
Volker Schnecke,
Robert J. Unwin,
Anna Walentinsson,
Carl Whatling,
Everson Nogoceke,
Gonzalo Durán Pacheco,
Ivan Formentini,
Thomas H. Schindler,
Piero Tortoli,
Luca Bassi,
Enrico Boni,
Alessandro Dallai,
Francesco Guidi,
Matteo Lenge,
Riccardo Matera,
Alessandro Ramalli,
Stefano Ricci,
Jacopo Viti,
Bernd Jablonka,
D Crowther,
Johann Gassenhuber,
Sibylle Hess,
Thomas Hübschle,
HansPaul Juretschke,
Hartmut Rütten,
Thorsten Sadowski,
Paulus Wohlfart,
Julia Brosnan,
Valérie Clerin,
Craig Hyde,
Anders Mälarstig,
Nick Pullen,
Mera Tilley,
Theresa Tuthill,
Ciara Vangjeli
Publication year - 2018
Publication title -
diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.219
H-Index - 330
eISSN - 1939-327X
pISSN - 0012-1797
DOI - 10.2337/db17-0914
Subject(s) - type 2 diabetes , genome wide association study , medicine , genetic association , disease , diabetes mellitus , bioinformatics , single nucleotide polymorphism , genetics , biology , endocrinology , genotype , gene
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.
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