Shared and Distinct Genetic Variants in Type 1 Diabetes and Celiac Disease

Deborah J. Smyth, Vincent Plagnol, Neil M. Walker, Jason D. Cooper, Kate Downes, Jennie H. M. Yang, Joanna M. M. Howson, Helen Stevens, Ross McManus, Cisca Wijmenga, Graham A. Heap, Patrick C. Dubois, David G. Clayton, Karen A. Hunt, David A. van Heel, John A. Todd*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

526 Citations (Scopus)

Abstract

Background: Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared.

Methods: We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects.

Results: Three celiac disease loci - RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25 - were associated with type 1 diabetes (P

Conclusions: A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.

Original languageEnglish
Pages (from-to)2767-2777
Number of pages11
JournalNew England Journal of Medicine
Volume359
Issue number26
Publication statusPublished - 25-Dec-2008

Keywords

  • GENOME-WIDE ASSOCIATION
  • INTESTINAL MICROBIOTA
  • RHEUMATOID-ARTHRITIS
  • RISK VARIANTS
  • SUSCEPTIBILITY
  • CHEMOKINE
  • MELLITUS
  • POLYMORPHISMS
  • PREVALENCE
  • MULTIPLE

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