Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families | Zendy

Markus Hippich | Zendy; Andreas Beyerlein | Zendy; William Hagopian | Zendy; Jeffrey P. Krischer | Zendy; Kendra Vehik | Zendy; Jan Knoop | Zendy; Christiane Winker | Zendy; Jorma Toppari | Zendy; Åke Lernmark | Zendy; Marian Rewers | Zendy; Andrea K. Steck | Zendy; JinXiong She | Zendy; Beena Akolkar | Zendy; Catherine C. Robertson | Zendy; Suna Önengüt-Gümüşcü | Zendy; Stephen S. Rich | Zendy; Ezio Bonifacio | Zendy; AnetteG. Ziegler | Zendy; Kimberly Bautista | Zendy; Judith Baxter | Zendy; Daniel Felipe-Morales | Zendy; Kimberly A. Driscoll | Zendy; Brigitte I. Frohnert | Zendy; Marisa Gallant | Zendy; Patricia Gesualdo | Zendy; Michelle Hoffman | Zendy; Rachel Karban | Zendy; Edwin Liu | Zendy; Jill M. 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Open Access

Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families

Author(s) -

Markus Hippich,

Andreas Beyerlein,

William Hagopian,

Jeffrey P. Krischer,

Kendra Vehik,

Jan Knoop,

Christiane Winker,

Jorma Toppari,

Åke Lernmark,

Marian Rewers,

Andrea K. Steck,

JinXiong She,

Beena Akolkar,

Catherine C. Robertson,

Suna Önengüt-Gümüşcü,

Stephen S. Rich,

Ezio Bonifacio,

AnetteG. Ziegler,

Kimberly Bautista,

Judith Baxter,

Daniel Felipe-Morales,

Kimberly A. Driscoll,

Brigitte I. Frohnert,

Marisa Gallant,

Patricia Gesualdo,

Michelle Hoffman,

Rachel Karban,

Edwin Liu,

Jill M. Norris,

Adela Samper-Imaz,

Kathleen Waugh,

Hali Wright,

Olli Simell,

Annika Adamsson,

Suvi Ahonen,

Heikki Hyöty,

Jorma Ilonen,

Mirva Koreasalo,

Kalle Kurppa,

Tiina Latva-aho,

Maria Lönnrot,

Markus Mattila,

Elina Mäntymäki,

Katja Multasuo,

Tiiininen,

Sari Niinistö,

Mia Nyblom,

Paula Ollikainen,

Petra Rajala,

Jenna Rautanen,

Anne Riikonen,

Minna Romo,

Suvi T. Ruohonen,

Juulia Rönkä,

Sini Vainionpää,

Eeva Varjonen,

Riitta Veijola,

Suvi Μ. Virtanen,

Mari Vähä-Mäkilä,

Iris Erlund,

Katri Lindfors,

Jin-Xiong She,

Desmond Schatz,

Diane Hopkins,

Leigh Steed,

Jennifer Bryant,

Janey Adams,

Katherine Silvis,

Michael J. Haller,

Melissa Gardiner,

Richard McIndoe,

Ashok Sharma,

Stephen W. Anderson,

Laura M. Jacobsen,

John Marks,

P.D. Towe,

Anette G. Ziegler,

Anita Gavrisan,

Cigdem Gezginci,

Anja Heublein,

Michael Hummel,

Sandra Hummel,

Annette Knopff,

Charlotte Koch,

Sibylle Koletzko,

Claudia Ramminger,

Roswith Roth,

Marlon Scholz,

Joanna Stock,

Katharina Warncke,

Lorena Wendel,

Christiane Winkler,

Daniel Agardh,

Carin Andrén Aronsson,

Maria Ask,

Jenny Bremer,

Ulla-Marie Carlsson,

Corrado Cilio,

Emelie Ericson- Hallström,

Annika Fors,

Lina Fransson,

Fredrik Johansen,

Berglind Jónsdóttir,

Silvija Jović,

Helena Elding Larsson,

Marielle Lindström,

Markus Lundgren,

Maria Månsson-Martinez,

Maria Markan,

Jessica Melin,

Zeliha Mestan,

Caroline Nilsson,

Karin Ottoson,

Kobra Rahmati,

Anita Ramelius,

Falastin Salami,

Sara Sibthorpe,

Anette Sjöberg,

Birgitta Janerot-Sjöberg,

Carina Törn,

Anne Wallin,

Åsa Wimar,

Sofie Åberg,

Michael Killian,

Claire Cowen Crouch,

Jennifer Skidmore,

Ashley Akramoff,

Jana Banjanin,

Masumeh Chavoshi,

Kayleen Dunson,

Rachel Hervey,

Rachel Lyons,

Arlene Meyer,

Denise Mulenga,

Jared Radtke,

Davey Schmitt,

Julie Schwabe,

Sarah Zink,

Dorothy Becker,

Margaret Franciscus,

MaryEllen Dalmagro-Elias Smith,

Ashi Daftary,

Mary Beth Klein,

Chrystal Yates,

Sarah Austin-Gonzalez,

Maryouri Avendano,

Sandra Baethke,

Rasheedah Brown,

Brant Burkhardt,

Martha Butterworth,

Joanna Clasen,

David Cuthbertson,

Christopher Eberhard,

Steven Fiske,

Dena Garcia,

Jennifer Garmeson,

Veena Gowda,

Kathleen Heyman,

Belinda Hsiao,

Francisco Perez Laras,

HyeSeung Lee,

Shu Liu,

Xiang Liu,

Kristian Lynch,

Colleen Maguire,

Jamie Malloy,

Cristina McCarthy,

Aubrie Merrell,

Steven Meulemans,

Hemang Parikh,

Ryan Quigley,

Cassandra Remedios,

Chris Shaffer,

Laura Smith,

Susan Smith,

Noah Sulman,

Roy Tamura,

Ulla Uusitalo,

Ponni Vijayakandipan,

Keith Wood,

Jimin Yang,

Michael Abbondondolo,

Lori Ballard,

David Hadley,

Wendy McLeod,

Kasia Bourcier,

Thomas Briese,

Suzanne Bennett Johnson,

Eric W. Triplett,

Liping Yu,

Dongmei Miao,

Polly J. Bingley,

Alistair J.K. Williams,

Kyla Chandler,

Olivia Ball,

Ilana Kelland,

Sian Grace,

Ben Gillard,

M Kellis,

Steven J. Mack,

Anna Lisa Fear,

WeiMin Chen,

Emily Farber,

Rebecca Roche Pickin,

Jonathan M. Davis,

Jordan Davis,

Dan Gallo,

Jessica Bonnie,

Paul Campolieto,

Sandra Ke,

Niveen Mulholland

Publication year - 2019

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/db18-0882

Subject(s) - type 2 diabetes , type 1 diabetes , population , genetic predisposition , diabetes mellitus , medicine , genotype , cohort , human leukocyte antigen , hazard ratio , first degree relatives , autoimmunity , immunology , genetics , family history , biology , endocrinology , gene , disease , antigen , confidence interval , environmental health

The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes ( n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, BTNL2 , was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6-3.02]) and for diabetes (HR 2.92 [95% CI 2.05-4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.

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