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

Todd, J. A., Walker, N. M., Cooper, J. D. , Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., Field, S. F., Payne, F., Lowe, C. E., Szeszko, J. S., Hafler, J. P., Zeitels, L., Yang, J. H. M., Vella, A., Nutland, S., Stevens, H. E., Schuilenburg, H., Coleman, G., Maisuria, M., Meadows, W., Smink, L. J., Healy, B., Burren, O. S., Lam, A. A. C., Ovington, N. R., Allen, J., Adlem, E., Leung, H-T., Wallace, C., Howson, J. M. M., Guja, C., Ionescu-Tırgoviste, C., Genetics of T1D in Finland, ., Simmonds, M. J., Heward, J. M., Gough, S. C. L., WTCCC, ., Dunger, D. B., Wicker, L. S. and Clayton, D. G. (2007) Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nature Genetics, 39 (7). pp. 857-864. ISSN 1061-4036

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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 smaller than 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 (P follow-up smaller than or equal to 1.35 x 10 -9; P overall smaller than or equal to 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. © 2007 Nature Publishing Group.

Keywords:article, chromosome, chromosome 18q, controlled study, gene locus, genome analysis, human, insulin dependent diabetes mellitus, major clinical study, priority journal, single nucleotide polymorphism, thyroid disease, Adolescent, Case-Control Studies, Chromosome Mapping, Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, Genome, Human, Humans, Polymorphism, Single Nucleotide
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22627
Deposited On:19 Mar 2016 22:55

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