TY - JOUR
T1 - Common and Unique Susceptibility Loci in Graves and Hashimoto Diseases
T2 - Results of Whole-Genome Screening in a Data Set of 102 Multiplex Families
AU - Tomer, Yaron
AU - Ban, Yoshiyuki
AU - Conception, Erlinda
AU - Barbesino, Giuseppe
AU - Villanueva, Ronald
AU - Greenberg, David A.
AU - Davies, Terry F.
N1 - Funding Information:
We thank all the families with AITD, who graciously agreed to participate in the study. Family enrollment was achieved through the collaboration of an International Consortium for the Genetics of Autoimmune Thyroid Disease (ICGA). Members of the ICGA included Drs. Luca Chiovato and Aldo Pinchera (Pisa), Sandra McLachlan (Los Angeles), Bernard Rees Smith (Cardiff, Wales), Fred Clark and Eric Young (Newcastle upon Tyne), Meir Berezin (Tel-Hashomer, Israel), George Carayanniotis (Newfoundland, Canada), and Rhoda Cobin (New York, New York). This work was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grants DK35764, DK45011, and DK52464 (to T.F.D.), grants DK61659 and DK58072 (to Y.T.), and grants DK31775, NS27941, and MH48858 (to D.A.G.).
PY - 2003/10/1
Y1 - 2003/10/1
N2 - The autoimmune thyroid diseases (AITDs), comprising Graves disease (GD) and Hashimoto thyroiditis (HT), develop as a result of a complex interaction between predisposing genes and environmental triggers. Previously, we identified six loci that showed evidence for linkage with AITD in a data set of 56 multiplex families. The goals of the present study were to replicate/reject the previously identified loci before fine mapping and sequencing the candidate genes in these regions. We performed a whole-genome linkage study in an expanded data set of 102 multiplex families with AITD (540 individuals), through use of 400 microsatellite markers. Seven loci showed evidence for linkage to AITD. Three loci, on chromosomes 6p, 8q, and 10q, showed evidence for linkage with both GD and HT (maximum multipoint heterogeneity LOD scores [HLOD] 2.0, 3.5, and 4.1, respectively). Three loci showed evidence for linkage with GD: on 7q (HLOD 2.3), 14q (HLOD 2.1), and 20q (LOD 3.3, in a subset of the families). One locus on 12q showed evidence of linkage with HT, giving an HLOD of 3.4. Comparison with the results obtained in the original data set showed that the 20q (GD-2) and 12q (HT-2) loci continued to show evidence for linkage in the expanded data set; the 6p and 14q loci were located within the same region as the previously identified 6p and 14q loci (AITD-1 and GD-1, respectively), but the Xq (GD-3) and 13q (HT-1) loci were not replicated in the expanded data set. These results demonstrated that multiple genes may predispose to GD and HT and that some may be common to both diseases and some are unique. The loci that continue to show evidence for linkage in the expanded data set represent serious candidate regions for gene identification.
AB - The autoimmune thyroid diseases (AITDs), comprising Graves disease (GD) and Hashimoto thyroiditis (HT), develop as a result of a complex interaction between predisposing genes and environmental triggers. Previously, we identified six loci that showed evidence for linkage with AITD in a data set of 56 multiplex families. The goals of the present study were to replicate/reject the previously identified loci before fine mapping and sequencing the candidate genes in these regions. We performed a whole-genome linkage study in an expanded data set of 102 multiplex families with AITD (540 individuals), through use of 400 microsatellite markers. Seven loci showed evidence for linkage to AITD. Three loci, on chromosomes 6p, 8q, and 10q, showed evidence for linkage with both GD and HT (maximum multipoint heterogeneity LOD scores [HLOD] 2.0, 3.5, and 4.1, respectively). Three loci showed evidence for linkage with GD: on 7q (HLOD 2.3), 14q (HLOD 2.1), and 20q (LOD 3.3, in a subset of the families). One locus on 12q showed evidence of linkage with HT, giving an HLOD of 3.4. Comparison with the results obtained in the original data set showed that the 20q (GD-2) and 12q (HT-2) loci continued to show evidence for linkage in the expanded data set; the 6p and 14q loci were located within the same region as the previously identified 6p and 14q loci (AITD-1 and GD-1, respectively), but the Xq (GD-3) and 13q (HT-1) loci were not replicated in the expanded data set. These results demonstrated that multiple genes may predispose to GD and HT and that some may be common to both diseases and some are unique. The loci that continue to show evidence for linkage in the expanded data set represent serious candidate regions for gene identification.
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U2 - 10.1086/378588
DO - 10.1086/378588
M3 - Article
C2 - 12973666
AN - SCOPUS:0142059659
SN - 0002-9297
VL - 73
SP - 736
EP - 747
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -