Shared and Distinct Genetic Variants in Type 1 Diabetes and Celiac Disease
By D. Smyth, V. Plagnol, N. Walker, J. Cooper, K. Downes, Jennie H. M. Yang, J. Howson, H. Stevens, R. McManus, C. Wijmenga and 6 more. New England Journal of Medicine, 2008
701 citations recorded by the source corpus.
BACKGROUND The inflammatory disorders type 1 diabetes (T1D) and celiac disease co-segregate in populations, suggesting a common genetic origin. Both are associated with the HLA class II genes on chromosome 6p21, and the present paper tested whether non-HLA loci are shared. METHODS We evaluated eight celiac disease risk loci in T1D by genotyping and statistical analyses of 8,064 T1D cases, 9,339 controls and 2,519 families. We also investigated 18 T1D loci in 2,560 celiac disease cases and 9,339 controls. RESULTS Three celiac disease loci, listed as chromosome/candidate gene: 1q31/RGS1, 2q12/IL18RAP and 6q25/TAGAP, were associated with T1D (P < 10−4). The 3p21/CCR5 32 base pair insertion/deletion variant was newly identified as a T1D locus (P = 1.81 × 10−8), and was also associated with celiac disease, as were 18p11/PTPN2 and 2q33/CTLA4, bringing the total loci shared to seven, including 12q24/SH2B3. The 2q12/IL18RAP and 6q25/TAGAP allele associations were in the opposite direction in T1D as compared to celiac disease. Distinct effects included 11p15/INS, 10p15/IL2RA and 1q13/PTPN22 in T1D and 3q25/IL12A and 3q28/LPP in celiac disease. CONCLUSIONS Genetic susceptibility to T1D and celiac disease shares common alleles. These data suggest that common biological mechanisms, such as autoimmunity related tissue damage and intolerance to dietary antigens may be a feature of T1D.
Subfields: Gastroenterology, Genetics, Rheumatology
View Paper: https://www.semanticscholar.org/paper/24b5f9c302b9a394ea91d111558abfb6b987f7c1
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Citations in the corpus
- New IBD genetics: common pathways with other diseases (2011, result): “This is in contrast to the clear increased incidence of coeliac disease in TIDM (but not T2DM), an observation that led to the identification of seven shared susceptibility loci between the two diseases (including RGS1, IL18RAP, TAGAP, PTPN2, CTLA4 and SH2B3).(120) In the Kaiser Permanente Medical C”
- Genome-wide association study of blood pressure and hypertension (2009, background): “This SNP has recently also been found to be reproducibly associated with type 1 diabetes mellitus and celiac diseas”
- Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease (2011, neutral): “76 189,587,750–189,602,595 (8; 15) Intron 2 of LPP”
- Multiple common variants for celiac disease influencing immune gene expression (2010, positive): “We previously showed that there is considerable overlap between risk loci for celiac disease and type 1 diabete”