A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease

J. C. Taylor, S. C. Gough, P. J. Hunt, T. H. Brix, K. Chatterjee, J. M. Connell, J. A. Franklyn, L. Hegedus, B. G. Robinson, W. M. Wiersinga, J. A.H. Wass, D. Zabaneh, I. Mackay, A. P. Weetman

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Context: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. Objective: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. Design: The study design was a genome-wide screen performed on affected relative pairs with AITD. Setting: Patients were recruited through hospital endocrinology clinics. Participants: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. Intervention: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. Main Outcome Measure: The study aimed to identify regions of genetic linkage to AITD. Results: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. Conclusions: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD. Copyright © 2006 by The Endocrine Society.
Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number2
DOIs
Publication statusPrint publication - Feb 2006
Externally publishedYes

Fingerprint

Thyroid Diseases
Autoimmune Diseases
Genes
Genome
Genetic Predisposition to Disease
Genetic Linkage
Graves Disease
Self Tolerance
Endocrinology
HLA Antigens
Thyroid Gland
Chromosomes
Ports and harbors
Outcome Assessment (Health Care)
Antigens
Blood
DNA

Cite this

Taylor, J. C., Gough, S. C., Hunt, P. J., Brix, T. H., Chatterjee, K., Connell, J. M., ... Weetman, A. P. (2006). A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease. Journal of Clinical Endocrinology and Metabolism, 91(2), 646-653. https://doi.org/10.1210/jc.2005-0686
Taylor, J. C. ; Gough, S. C. ; Hunt, P. J. ; Brix, T. H. ; Chatterjee, K. ; Connell, J. M. ; Franklyn, J. A. ; Hegedus, L. ; Robinson, B. G. ; Wiersinga, W. M. ; Wass, J. A.H. ; Zabaneh, D. ; Mackay, I. ; Weetman, A. P. / A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 2. pp. 646-653.
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abstract = "Context: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. Objective: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. Design: The study design was a genome-wide screen performed on affected relative pairs with AITD. Setting: Patients were recruited through hospital endocrinology clinics. Participants: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. Intervention: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. Main Outcome Measure: The study aimed to identify regions of genetic linkage to AITD. Results: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. Conclusions: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD. Copyright {\circledC} 2006 by The Endocrine Society.",
author = "Taylor, {J. C.} and Gough, {S. C.} and Hunt, {P. J.} and Brix, {T. H.} and K. Chatterjee and Connell, {J. M.} and Franklyn, {J. A.} and L. Hegedus and Robinson, {B. G.} and Wiersinga, {W. M.} and Wass, {J. A.H.} and D. Zabaneh and I. Mackay and Weetman, {A. P.}",
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Taylor, JC, Gough, SC, Hunt, PJ, Brix, TH, Chatterjee, K, Connell, JM, Franklyn, JA, Hegedus, L, Robinson, BG, Wiersinga, WM, Wass, JAH, Zabaneh, D, Mackay, I & Weetman, AP 2006, 'A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 2, pp. 646-653. https://doi.org/10.1210/jc.2005-0686

A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease. / Taylor, J. C.; Gough, S. C.; Hunt, P. J.; Brix, T. H.; Chatterjee, K.; Connell, J. M.; Franklyn, J. A.; Hegedus, L.; Robinson, B. G.; Wiersinga, W. M.; Wass, J. A.H.; Zabaneh, D.; Mackay, I.; Weetman, A. P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 2, 02.2006, p. 646-653.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease

AU - Taylor, J. C.

AU - Gough, S. C.

AU - Hunt, P. J.

AU - Brix, T. H.

AU - Chatterjee, K.

AU - Connell, J. M.

AU - Franklyn, J. A.

AU - Hegedus, L.

AU - Robinson, B. G.

AU - Wiersinga, W. M.

AU - Wass, J. A.H.

AU - Zabaneh, D.

AU - Mackay, I.

AU - Weetman, A. P.

PY - 2006/2

Y1 - 2006/2

N2 - Context: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. Objective: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. Design: The study design was a genome-wide screen performed on affected relative pairs with AITD. Setting: Patients were recruited through hospital endocrinology clinics. Participants: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. Intervention: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. Main Outcome Measure: The study aimed to identify regions of genetic linkage to AITD. Results: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. Conclusions: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD. Copyright © 2006 by The Endocrine Society.

AB - Context: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. Objective: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. Design: The study design was a genome-wide screen performed on affected relative pairs with AITD. Setting: Patients were recruited through hospital endocrinology clinics. Participants: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. Intervention: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. Main Outcome Measure: The study aimed to identify regions of genetic linkage to AITD. Results: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. Conclusions: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD. Copyright © 2006 by The Endocrine Society.

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U2 - 10.1210/jc.2005-0686

DO - 10.1210/jc.2005-0686

M3 - Article

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EP - 653

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JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

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