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A Genome-Wide Screen in 1119 Relative Pairs with Autoimmune Thyroid Disease

Oxagen Ltd. (J.C.T., D.Z., I.M.), Abingdon, Oxon OX14 4RY, United Kingdom; Oxford Genetics Knowledge Park, Wellcome Trust Center for Human Genetics (J.C.T.), Headington, Oxford OX3 7BN, United Kingdom; Department of Medicine, Division of Medical Sciences, University of Birmingham (S.C.G., J.A.F.), Birmingham B15 2TT, United Kingdom; Department of Endocrinology, Christchurch Hospital (P.J.H.), Christchurch 8001, New Zealand; Department of Endocrinology and Metabolism, Odense University Hospital (T.H.B., L.H.), DK-5000 Odense C, Denmark; Department of Medicine, Addenbrooke’s Hospital (K.C.), Cambridge CB2 2QQ, United Kingdom; University Department of Medicine and Therapeutics, Western Infirmary (J.M.C.), Glasgow, Scotland G11 6NT, United Kingdom; Kolling Institute and Department of Endocrinology, Royal North Shore Hospital, University of Sydney (B.G.R.), Sydney, NSW 2065, Australia; Department of Endocrinology, University Hospital Academisch Medisch Centrum, University of Amsterdam (W.M.W.), 1100 DE Amsterdam, The Netherlands; Department of Endocrinology, Oxford Center for Diabetes, Endocrinology, and Metabolism, Churchill Hospital (J.A.H.W.), Oxford OX3 7LJ, United Kingdom; and University of Sheffield Clinical Sciences Center, Northern General Hospital (A.P.W.), Sheffield S5 7AU, United Kingdom

Address all correspondence and requests for reprints to: Dr. J. C. Taylor, Oxford Genetics Knowledge Park, Wellcome Trust Center for Human Genetics, Roosevelt Drive, Headington, Oxford OX3 7BN, United Kingdom. E-mail: jenny.taylor{at}well.ox.ac.uk.

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.

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