A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in I… (2024)

https://doi.org/10.2337/dc18-0087 · Повний текст

Видання: Diabetes Care, 2018, №9, с.1887-1894

Видавець: American Diabetes Association

Автори:

Maria J. Redondo
Susan Geyer
Andrea K. Steck
Seth Sharp
John M. Wentworth
Michael N. Weedon
Peter Antinozzi
Jay Sosenko
Mark Atkinson
Alberto Pugliese
Richard A. Oram
P. Antinozzi
M. Atkinson
M. Battaglia
D. Becker
P. Bingley
E. Bosi
J. Buckner
P. Colman
P. Gottlieb
K. Herold
R. Insel
T. Kay
M. Knip
J.B. Marks
A. Moran
J. Palmer
M. Peakman
L. Philipson
A. Pugliese
P. Raskin
H. Rodriguez
B. Roep
W. Russell
D.A. Schatz
D. Wherrett
D. Wilson
W. Winter
A. Ziegler
C. Benoist
J. Blum
P. Chase
M. Clare-Salzler
R. Clynes
G. Eisenbarth
C.G. Fathman
G. Grave
B. Hering
F. Kaufman
E. Leschek
J. Mahon
K. Nanto-Salonen
G. Nepom
T. Orban
R. Parkman
M. Pescovitz
J. Peyman
M. Roncarolo
O. Simell
R. Sherwin
M. Siegelman
A. Steck
J. Thomas
M. Trucco
J. Wagner
, Carla J. Greenbaum
Katarzyna Bourcier
Richard Insel
Jeffrey P. Krischer
Ellen Leschek
Lisa Rafkin
Lisa Spain
Catherine Cowie
Mary Foulkes
Heidi Krause-Steinrauf
John M. Lachin
Saul Malozowski
John Peyman
John Ridge
Peter Savage
Jay S. Skyler
Stephanie J. Zafonte
Norma S. Kenyon
Irene Santiago
Jay M. Sosenko
Brian Bundy
Michael Abbondondolo
Timothy Adams
Darlene Amado
Ilma Asif
Matthew Boonstra
Brian Bundy
Cristina Burroughs
David Cuthbertson
Mary Deemer
Christopher Eberhard
Steve Fiske
Julie Ford
Jennifer Garmeson
Heather Guillette
Susan Geyer
Brian Hays
Courtney Henderson
Martha Henry
Kathleen Heyman
Belinda Hsiao
Christina Karges
Nichole Keaton
Amanda Kinderman
Pat Law
Ashely Leinbach
Cristin Linton
Shu Liu
Jennifer Lloyd
Jamie Malloy
Kristin Maddox
Julie Martin
Jessica Miller
Eric Milliot
Margaret Moore
Sarah Muller
Thuy Nguyen
Ryan O’Donnell
Vanessa Oduah
Jennifer Pilger
Amy Roberts
Kelly Sadler
Tina Stavros
Roy Tamura
Keith Wood
Ping Xu
Kenneth Young
Persida Alies
Franz Badias
Aaron Baker
Monica Bassi
Craig Beam
David Boulware
London Bounmananh
Susan Bream
Doug Freeman
Jessica Gough
Jinin Ginem
Moriah Granger
Mary Holloway
Michelle Kieffer
Page Lane
Lavanya Nallamshetty
Yazandra Parrimon
Kate Paulus
Joy Ramiro
AQesha Luvon Ritzie
Archana Sharma
Audrey Shor
Xiaohong Song
Amanda Terry
Jeanne Weinberger
Margaret Wootten
Pamela Harding
Susan McDonough
Paula F. McGee
Kimberly Owens Hess
Donna Phoebus
Scott Quinlan
Erica Raiden
Emily Batts
Chris Buddy
Kristin Kirpatrick
Mary Ramey
Ann Shultz
Chris Webb
Melita Romesco
Judith Fradkin
Emily Blumberg
Gerald Beck
David Brillon
Rose Gubitosi-Klug
Lori Laffel
Robert Veatch
Dennis Wallace
Jonathan Braun
Ake Lernmark
Bernard Lo
Herman Mitchell
Ali Naji
Jorn Nerup
Trevor Orchard
Michael Steffes
Anastasios Tsiatis
Bernard Zinman
Brett Loechelt
Lindsey Baden
Michael Green
Adriana Weinberg
Santica Marcovina
Jerry P. Palmer
Adriana Weinberg
Liping Yu
Sunanda Babu
William Winter
George S. Eisenbarth
Polly Bingley
Raphael Clynes
Linda DiMeglio
George Eisenbarth
Brian Hays
Jennifer Marks
Della Matheson
Henry Rodriguez
Darrell Wilson
Maria J. Redondo
David Gomez
Xiati Zheng
Sandra Pena
Massimo Pietropaolo
Emily Batts
Tyler Brown
Jane Buckner
Angela Dove
Marissa Hammond
Deborah Hefty
Jani Klein
Kristen Kuhns
McKenzie Letlau
Sandra Lord
Marli McCulloch-Olson
Lisa Miller
Gerald Nepom
Jared Odegard
Mary Ramey
Elaine Sachter
Marissa St. Marie
Kimberly Stickney
Dana VanBuecken
Ben Vellek
Christine Webber
Laurie Allen
Jenna Bollyk
Nicole Hilderman
Hebatullah Ismail
Steve Lamola
Srinath Sanda
Heather Vendettuoli
David Tridgell
Roshanak Monzavi
Meredith Bock
Lynda Fisher
Mary Halvorson
Debra Jeandron
Mimi Kim
Jamie Wood
Mitchell Geffner
Francine Kaufman
Robertson Parkman
Christine Salazar
Robin Goland
Raphael Clynes
Steve Cook
Matthew Freeby
Mary Pat Gallagher
Rachelle Gandica
Ellen Greenberg
Amy Kurland
Sarah Pollak
Amy Wolk
Mary Chan
Linda Koplimae
Elizabeth Levine
Kelly Smith
Jeniece Trast
Linda DiMeglio
Janice Blum
Carmella Evans-Molina
Robin Hufferd
Bonnie Jagielo
Christy Kruse
Vanessa Patrick
Mark Rigby
Maria Spall
Kim Swinney
Jennifer Terrell
Lyla Christner
LeeAnn Ford
Sheryl Lynch
Martha Menendez
Patricia Merrill
Mark Pescovitz
Henry Rodriguez
Cielo Alleyn
David Baidal
Steve Fay
Jason Gaglia
Brittany Resnick
Sarah Szubowicz
Gordon Weir
Ronald Benjamin
Debbie Conboy
Andrea deManbey
Richard Jackson
Heyam Jalahej
Tihmar Orban
Alyne Ricker
Joseph Wolfsdorf
Hui H. Zhang
Darrell Wilson
Tandy Aye
Bonita Baker
Karen Barahona
Bruce Buckingham
Kerry Esrey
Trudy Esrey
Garry Fathman
Radhika Snyder
Beenu Aneja
Maya Chatav
Oralia Espinoza
Eliana Frank
Jenny Liu
Jennifer Perry
Rebecca Pyle
Alison Rigby
Kristin Riley
Adriana Soto
Stephen Gitelman
Saleh Adi
Mark Anderson
Ashley Berhel
Kathy Breen
Kathleen Fraser
Andrea Gerard-Gonzalez
Paula Jossan
Robert Lustig
Sara Moassesfar
Amy Mugg
David Ng
Priya Prahalod
Martha Rangel-Lugo
Srinath Sanda
Joshua Tarkoff
Christine Torok
Rebecca Wesch
Ivy Aslan
Jeanne Buchanan
Jennifer Cordier
Celia Hamilton
Louise Hawkins
Thu Ho
Anjali Jain
Karen Ko
Theresa Lee
Shelly Phelps
Stephen Rosenthal
Taninee Sahakitrungruang
Lorraine Stehl
Lisa Taylor
Marcia Wertz
Jenise Wong
Louis Philipson
Rosemary Briars
Nancy Devine
Elizabeth Littlejohn
Tiffany Grant
Peter Gottlieb
Georgeanna Klingensmith
Andrea Steck
Aimon Alkanani
Kimberly Bautista
Ruth Bedoy
Aaron Blau
Betsy Burke
Laraine Cory
MyLinh Dang
Lisa Fitzgerald-Miller
Alex Fouts
Vicky Gage
Satish Garg
Patricia Gesauldo
Raymond Gutin
Cory Hayes
Michelle Hoffman
Kaitlin Ketchum
Nyla Logsden-Sackett
David Maahs
Laurel Messer
Lisa Meyers
Aaron Michels
Stesha Peaco*ck
Marian Rewers
Perla Rodriguez
Flor Sepulbeda
Rachel Sippl
Andrea Steck
Iman Taki
Bao-Khan Tran
Tuan Tran
R. Paul Wadwa
Philip Zeitler
Jennifer Barker
Sandra Barry
Laurie Birks
Leah Bomsburger
Terra Bookert
Leah Briggs
Patricia Burdick
Rosio Cabrera
Peter Chase
Erin Cobry
Amy Conley
Gabrielle Cook
Joseph Daniels
Dominic DiDomenico
Jennifer Eckert
Angelica Ehler
George Eisenbarth
Pamela Fain
Rosanna Fiallo-Scharer
Nicole Frank
Hannah Goettle
Michelle Haarhues
Sherrie Harris
Lauren Horton
John Hutton
Joy Jeffrrey
Rachael Jenison
Kelly Jones
Whitney Kastelic
Maria Amelia King
Debbie Lehr
Jenna Lungaro
Kendra Mason
Heather Maurer
Luy Nguyen
Allison Proto
Jaime Realsen
Kristina Schmitt
Mara Schwartz
San Skovgaard
Jennifer Smith
Brandon Vanderwel
Mary Voelmle
Rebecca Wagner
Amy Wallace
Philip Walravens
Laurie Weiner
Becky Westerhoff
Emily Westfall
Katina Widmer
Hali Wright
Desmond Schatz
Annie Abraham
Mark Atkinson
Miriam Cintron
Michael Clare-Salzler
Jessica Ferguson
Michael Haller
Jennifer Hosford
Diane Mancini
Hank Rohrs
Janet Silverstein
Jamie Thomas
William Winter
Gloria Cole
Roberta Cook
Ryan Coy
Elena Hicks
Nancy Lewis
Jennifer Marks
Alberto Pugliese
Carlos Blaschke
Della Matheson
Natalia Sanders-Branca
Jay Sosenko
Luz Arazo
Ray Arce
Mario Cisneros
Samir Sabbag
Antoinette Moran
Carrie Gibson
Brian Fife
Bernhard Hering
Christine Kwong
Janice Leschyshyn
Brandon Nathan
Beth Pappenfus
Anne Street
Mary Ann Boes
Sarah Peterson Eck
Lois Finney
Theresa Albright Fischer
Andrea Martin
Chenai Jacqueline Muzamhindo
Missy Rhodes
Jennifer Smith
John Wagner
Bryan Wood
Dorothy Becker
Kelli Delallo
Ana Diaz
Barbara Elnyczky
Ingrid Libman
Beata Pasek
Karen Riley
Massimo Trucco
Brian Copemen
Diane Gwynn
Frederico Toledo
Henry Rodriguez
Sureka Bollepalli
Frank Diamond
Emily Eyth
Danielle Henson
Anne Lenz
Dorothy Shulman
Phillip Raskin
Soumya Adhikari
Brian Dickson
Erin Dunnigan
Ildiko Lingvay
Lourdes Pruneda
Maria Ramos-Roman
Philip Raskin
Chanhaeng Rhee
John Richard
Mark Siegelman
Daytheon Sturges
Kathryn Sumpter
Perrin White
Marilyn Alford
Jamie Arthur
M. Larissa Aviles-Santa
Erica Cordova
Renee Davis
Stefani Fernandez
Steve Fordan
Tauri Hardin
Aris Jacobs
Polina Kaloyanova
Ivanna Lukacova-Zib
Sasan Mirfakhraee
Alok Mohan
Hiroshi Noto
Oralenda Smith
Nenita Torres
Diane Wherrett
Diana Balmer
Lesley Eisel
Roze Kovalakovska
Mala Mehan
Farah Sultan
Brenda Ahenkorah
Jose Cevallos
Natasha Razack
Mary Jo Ricci
Angela Rhode
Mithula Srikandarajah
Rachel Steger
William E. Russell
Margo Black
Faith Brendle
Anne Brown
Daniel Moore
Eric Pittel
Alyssa Robertson
April Shannon
James W. Thomas
Kevan Herold
Laurie Feldman
Robert Sherwin
William Tamborlane
Stuart Weinzimer
Jorma Toppari
Tiina Kallio
Maarit Kärkkäinen
Elina Mäntymäki
Tiina Niininen
Birgitta Nurmi
Petro Rajala
Minna Romo
Sointu Suomenrinne
Kirsti Näntö-Salonen
Olli Simell
Tuula Simell
Emanuele Bosi
Manuela Battaglia
Eleonora Bianconi
Riccardo Bonfanti
Pauline Grogan
Andrea Laurenzi
Sabina Martinenghi
Franco Meschi
Matteo Pastore
Luca Falqui
Maria Teresa Muscato
Matteo Viscardi
Harriet Castleden
Nicola Farthing
Sam Loud
Claire Matthews
Jennifer McGhee
Ann Morgan
Joanna Pollitt
Rebecca Elliot-Jones
Carole Wheaton
Mikael Knip
Heli Siljander
Heli Suomalainen
Peter Colman
Felicity Healy
Shelley Mesfin
Leanne Redl
John Wentworth
Jinny Willis
Maree Farley
Leonard Harrison
Christine Perry
Fiona Williams
A. Mayo
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L. Volin
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V. Viswanathan
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O. Kawadry
J.A. Olson
L. Patterson
T. Ahmad
B. Flores
D. Domek
S. Domek
K. Copeland
M. George
J. Less
T. Davis
M. Short
A. Dwarakanathan
P. O’Donnell
B. Boerner
L. Larson
M. Phillips
M. Rendell
K. Larson
C. Smith
K. Zebrowski
L. Kuechenmeister
M. Thevarayapillai
M. Daniels
H. Speer
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C. Reh
A. Bhangoo
P. Desrosiers
L. Ireland
T. Misla
C. Torres
S. Wells
J. Villar
M. Yu
D. Berry
D. Cook
J. Soder
A. Powell
M. Ng
M. Morrison
Z. Haslam
M. Lawson
B. Bradley
J. Courtney
C. Richardson
C. Watson
E. Keely
D. DeCurtis
M. Vaccarcello-Cruz
Z. Torres
K. Sandberg
H. Hsiang
B. Joy
D. McCormick
A. Powell
H. Jones
J. Bell
S. Hargadon
S. Hudson
M. Kummer
S. Sauder
E. Sutton
K. Gensel
R. Aguirre-Castaneda
V. Benavides Lopez
D. Hemp
S. Allen
J. Stear
E. Davis
T. Jones
A. Roberts
J.A. Dart
N. Paramalingam
L.E. Levitt Katz
N. Chaudhary
K.M. Murphy
S.M. Willi
B. Schwartzman
C. Kapadia
D. Larson
D. McClellan
G. Shaibai
L.A. Kelley
G. Villa
C. Kelley
R. Diamond
M. Kabbani
T. Dajani
F. Hoekstra
M. Magorno
J. Holst
V. Chauhan
N. Wilson
P. Bononi
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T. Noland
J. Brodksy
L. Bacon
J.B. Quintos
L.S. Topor
S. Bialo
B. Bancroft
A.G. Soto
W. Lagarde
H. Lockemer
T. Vanderploeg
M.A. Ibrahim
M. Huie
V. Sanchez
R. Edelen
R. Marchiando
J. Palmer
T. Repas
M. Wasson
P. Auker
J. Culbertson
T. Kieffer
D. Voorhees
T. Borgwardt
L. DeRaad
K. Eckert
E. Isaacson
H. Kuhn
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M. Schubert
G. Francis
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C. Leyva
K. Rivera
J. Padilla
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U. Nadgir
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G. Prakasam
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A. Yerka
T. Freels
J.M. Hassing
J. Webster
R. Green
P. Carter
J. Galloway
D. Hoelzer
S. Roberts
S. Said
P. Sullivan
H.F. Allen
E. Reiter
E. Feinberg
C. Johnson
L.A. Newhook
D. Hagerty
N.H. White
L. Levandoski
J. Kyllo
M. Johnson
C. Benoit
P. Iyer
F. Diamond
H. Hosono
S. Jackman
L. Barette
P. Jones
I. Sills
S. Bzdick
J. Bulger
R. Weinstock
I. Douek
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G. Modgill
G. Gyorffy
L. Robin
N. Vaidya
S. Crouch
K. O’Brien
C. Thompson
N. Thorne
J. Blumer
J. Kalic
L. Klepek
J. Paulett
B. Rosolowski
J. Horner
M. Watkins
J.L. Casey
K. Carpenter
C. Burns
J. Horton
C. Pritchard
D. Soetaert
A.G. Wynne
K. Kaiserman
M. Halvorson
C. Chin
O.Y. Molina
C. Patel
R. Senguttuvan
M. Wheeler
O. Furet
C. Steuhm
D.H. Jelley
S. Goudeau
L. Chalmers
D. Greer
C. Panagiotopoulos
D.L. Metzger
D. Nguyen
M. Horowitz
M.P. Christiansen
E. Glades
C. Morimoto
M. Macarewich
R. Norman
K. Patin
C. Vargas
A. Barbanica
A. Yu
P. Vaidyanathan
W. Osborne
R. Mehra
S. Kaster
S. Neace
J. Horner
G. Reeves
C. Cordrey
L. Marrs
T. Miller
S. Dowshen
D. Doyle
S. Walker
D. Catte
H. Dean
M. Drury-Brown
B. Hackman
M.M.C. Lee
S. Malkani
K. Cullen
K. Johnson
P. Hampton
M. McCarrell
C. Curtis
E. Paul
Y. Zambrano
Type 1 Diabetes TrialNet Study Group

Анотація

<jats:sec> OBJECTIVE We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. </jats:sec> <jats:sec> RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. </jats:sec> <jats:sec> RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS &gt;0.295, 95% CI 1.47–3.51; P = 0.0002). </jats:sec> <jats:sec> CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives. </jats:sec>

Джерела фінансування

National Institute of Diabetes and Digestive and Kidney Diseases
Diabetes UK Harry Keen Fellowship

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