Todd, JA and Walker, NM and Cooper, JD and Smyth, DJ and Downes, K and Plagnol, V and Bailey, R and Nejentsev, S and Field, SF and Payne, F and Lowe, CE and Szeszko, JS and Hafler, JP and Zeitels, L and Yang, JHM and Vella, A and Nutland, S and Stevens, HE and Schuilenburg, H and Coleman, G and Maisuria, M and Meadows, W and Smink, LJ and Healy, B and Burren, OS and Lam, AAC and Ovington, NR and Allen, J and Adlem, E and Leung, HT and Wallace, C and Howson, JMM and Guja, C and Ionescu-Tirgoviste, C and Simmonds, MJ and Heward, JM and Gough, SCL and Dunger, DB and Wicker, LS and Clayton, DG and Genetics Type 1 Diabet Finland, and Wellcome Trust Case Control Consor, (2007) Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. NAT GENET , 39 (7) 857 - 864. 10.1038/ng2068.
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The Wellcome Trust Case Control Consortium ( WTCCC) primary genome- wide association ( GWA) scan(1) on seven diseases, including the multifactorial autoimmune disease type 1 diabetes ( T1D), shows associations at P < 5 x 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 similar to 10(-9); P-overall <= 1.15 x 10(-14)), leaving eight regions with small effects or false- positive associations. We also obtained evidence for chromosome 18q22 ( P-overall 1.38 x 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.
|Title:||Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes|
|Keywords:||TYROSINE-PHOSPHATASE, GENE, DISEASE, LOCUS, SNPS, SUSCEPTIBILITY, POLYMORPHISMS, AUTOIMMUNITY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment > UCL Genetics Institute|
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