CONTEXT: Genetic factors play a major role in the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). We have previously identified three loci on chromosomes 10q, 12q, and 14q that showed strong linkage with AITD, HT, and GD, respectively. OBJECTIVES: The objective of the study was to identify the AITD susceptibility genes at the 10q, 12q, and 14q loci. DESIGN AND PARTICIPANTS: Three hundred forty North American Caucasian AITD patients and 183 healthy controls were studied. The 10q, 12q, and 14q loci were fine mapped by genotyping densely spaced single-nucleotide polymorphisms (SNPs) using the Illumina GoldenGate genotyping platform. Case control association analyses were performed using the UNPHASED computer package. Associated SNPs were reanalyzed in a replication set consisting of 238 AITD patients and 276 controls. RESULTS: Fine mapping of the AITD locus, 10q, showed replicated association of the AITD phenotype (both GD and HT) with SNP rs6479778. This SNP was located within the ARID5B gene recently reported to be associated with rheumatoid arthritis and GD in Japanese. Fine mapping of the GD locus, 14q, revealed replicated association of the GD phenotype with two markers, rs12147587 and rs2284720, located within the NRXN3 and TSHR genes, respectively. CONCLUSIONS: Fine mapping of three linked loci identified novel susceptibility genes for AITD. The discoveries of new AITD susceptibility genes will engender a new understanding of AITD etiology.
CONTEXT: Genetic factors play a major role in the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). We have previously identified three loci on chromosomes 10q, 12q, and 14q that showed strong linkage with AITD, HT, and GD, respectively. OBJECTIVES: The objective of the study was to identify the AITD susceptibility genes at the 10q, 12q, and 14q loci. DESIGN AND PARTICIPANTS: Three hundred forty North American Caucasian AITD patients and 183 healthy controls were studied. The 10q, 12q, and 14q loci were fine mapped by genotyping densely spaced single-nucleotide polymorphisms (SNPs) using the Illumina GoldenGate genotyping platform. Case control association analyses were performed using the UNPHASED computer package. Associated SNPs were reanalyzed in a replication set consisting of 238 AITD patients and 276 controls. RESULTS: Fine mapping of the AITD locus, 10q, showed replicated association of the AITD phenotype (both GD and HT) with SNP rs6479778. This SNP was located within the ARID5B gene recently reported to be associated with rheumatoid arthritis and GD in Japanese. Fine mapping of the GD locus, 14q, revealed replicated association of the GD phenotype with two markers, rs12147587 and rs2284720, located within the NRXN3 and TSHR genes, respectively. CONCLUSIONS: Fine mapping of three linked loci identified novel susceptibility genes for AITD. The discoveries of new AITD susceptibility genes will engender a new understanding of AITD etiology.
Authors: Mihaela Stefan; Eric M Jacobson; Amanda K Huber; David A Greenberg; Cheuk Wun Li; Luce Skrabanek; Erlinda Conception; Mohammed Fadlalla; Kenneth Ho; Yaron Tomer Journal: J Biol Chem Date: 2011-07-12 Impact factor: 5.157
Authors: Elsie M Allen; Wen-Chi Hsueh; Mona M Sabra; Toni I Pollin; Paul W Ladenson; Kristi D Silver; Braxton D Mitchell; Alan R Shuldiner Journal: J Clin Endocrinol Metab Date: 2003-03 Impact factor: 5.958
Authors: Yaron Tomer; Yoshiyuki Ban; Erlinda Concepcion; Giuseppe Barbesino; Ronald Villanueva; David A Greenberg; Terry F Davies Journal: Am J Hum Genet Date: 2003-09-12 Impact factor: 11.025
Authors: Bryan M Dechairo; Delilah Zabaneh; Joanne Collins; Oliver Brand; Gary J Dawson; Angie P Green; Ian Mackay; Jayne A Franklyn; John M Connell; John A H Wass; Wilmar M Wiersinga; Laszlo Hegedus; Thomas Brix; Bruce G Robinson; Penny J Hunt; Anthony P Weetman; Alisoun H Carey; Stephen C Gough Journal: Eur J Hum Genet Date: 2005-11 Impact factor: 4.246
Authors: Yoshiyuki Ban; David A Greenberg; Terry F Davies; Eric Jacobson; Erlinda Concepcion; Yaron Tomer Journal: J Clin Endocrinol Metab Date: 2008-06-17 Impact factor: 5.958