Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes

By John A. Todd, N. Walker, J. Cooper, D. Smyth, K. Downes, V. Plagnol, R. A. Bailey, S. Nejentsev, Sarah F. Field, F. Payne and 30 more. Nature Genetics, 2007

1,532 citations recorded by the source corpus.

The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 × 10−7 between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (Pfollow-up ≤ 1.35 × 10−9; Poverall ≤ 1.15 × 10−14), leaving eight regions with small effects or false-positive associations. We also obtained evidence for chromosome 18q22 (Poverall = 1.38 × 10−8) from a GWA study of nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten.

Subfields: Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/15428b611f4dc565b437064d6d67ac0dfdc439e8

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Citations in the corpus

Mapping the Genetic Architecture of Gene Expression in Human Liver (2008, background): “Expression Traits Corresponding to Genes Implicated in the T1D WTCCC Study [14,15] See Table 2 for other HLA class II genes. a The gene was not implicated by the WTCCC study, but had expression values in the HLC that were associated with the indicated T1D SNP identified in the WTCCC study. b The…”
Regulatory T Cells and Human Disease. (2020, background): “Particular HLA alleles are associated with common autoimmune diseases, some alleles being autoimmune susceptible, others protective (135).”
Systems medicine: the future of medical genomics and healthcare (2009, background): “significant problems with signal-to-noise ratios that still severely limit the conclusions that can be drawn from such studies, progress has been made in identifying susceptibility loci involved in, for example, diabetes [161-163], obesity [164], and breast or lung cancer [165-167].”
A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci (2008, background): “As stated previously, this region needs to be resequenced thoroughly followed by comprehensive genotyping in larger numbers of samples to identify the autoimmune associated variant/s [45].”
STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement (2009, neutral): “org 0158 February 2009 | Volume 6 | Issue 2 | e1000022 association studies [85,87–105].”