Seven newly identified loci for autoimmune thyroid disease

doi:10.1093/hmg/dds357

. 2012 Dec 1;21(23):5202-8.

doi: 10.1093/hmg/dds357. Epub 2012 Aug 24.

Seven newly identified loci for autoimmune thyroid disease

Jason D Cooper¹, Matthew J Simmonds, Neil M Walker, Oliver Burren, Oliver J Brand, Hui Guo, Chris Wallace, Helen Stevens, Gillian Coleman; Wellcome Trust Case Control Consortium; Jayne A Franklyn, John A Todd, Stephen C L Gough

Collaborators, Affiliations

Collaborators

Wellcome Trust Case Control Consortium:
Jan Aerts, Tariq Ahmad, Hazel Arbury, Anthony Attwood, Adam Auton, Stephen G Ball, Anthony J Balmforth, Chris Barnes, Jeffrey C Barrett, Inês Barroso, Anne Barton, Amanda J Bennett, Sanjeev Bhaskar, Katarzyna Blaszczyk, John Bowes, Oliver J Brand, Peter S Braund, Francesca Bredin, Gerome Breen, Morris J Brown, Ian N Bruce, Jaswinder Bull, Oliver S Burren, John Burton, Jake Byrnes, Sian Caesar, Niall Cardin, Chris M Clee, Alison J Coffey, John M C Connell, Donald F Conrad, Jason D Cooper, Anna F Dominiczak, Kate Downes, Hazel E Drummond, Darshna Dudakia, Andrew Dunham, Bernadette Ebbs, Diana Eccles, Sarah Edkins, Cathryn Edwards, Anna Elliot, Paul Emery, David M Evans, Gareth Evans, Steve Eyre, Anne Farmer, I Nicol Ferrier, Edward Flynn, Alistair Forbes, Liz Forty, Jayne A Franklyn, Timothy M Frayling, Rachel M Freathy, Eleni Giannoulatou, Polly Gibbs, Paul Gilbert, Katherine Gordon-Smith, Emma Gray, Elaine Green, Chris J Groves, Detelina Grozeva, Rhian Gwilliam, Anita Hall, Naomi Hammond, Matt Hardy, Pile Harrison, Neelam Hassanali, Husam Hebaishi, Sarah Hines, Anne Hinks, Graham A Hitman, Lynne Hocking, Chris Holmes, Eleanor Howard, Philip Howard, Joanna M M Howson, Debbie Hughes, Sarah Hunt, John D Isaacs, Mahim Jain, Derek P Jewell, Toby Johnson, Jennifer D Jolley, Ian R Jones, Lisa A Jones, George Kirov, Cordelia F Langford, Hana Lango-Allen, G Mark Lathrop, James Lee, Kate L Lee, Charlie Lees, Kevin Lewis, Cecilia M Lindgren, Meeta Maisuria-Armer, Julian Maller, John Mansfield, Jonathan L Marchini, Paul Martin, Dunecan C O Massey, Wendy L McArdle, Peter McGuffin, Kirsten E McLay, Gil McVean, Alex Mentzer, Michael L Mimmack, Ann E Morgan, Andrew P Morris, Craig Mowat, Patricia B Munroe, Simon Myers, William Newman, Elaine R Nimmo, Michael C O'Donovan, Abiodun Onipinla, Nigel R Ovington, Michael J Owen, Kimmo Palin, Aarno Palotie, Kirstie Parnell, Richard Pearson, David Pernet, John R B Perry, Anne Phillips, Vincent Plagnol, Natalie J Prescott, Inga Prokopenko, Michael A Quail, Suzanne Rafelt, Nigel W Rayner, David M Reid, Anthony Renwick, Susan M Ring, Neil Robertson, Samuel Robson, Ellie Russell, David St Clair, Jennifer G Sambrook, Jeremy D Sanderson, Stephen J Sawcer, Helen Schuilenburg, Carol E Scott, Richard Scott, Sheila Seal, Sue Shaw-Hawkins, Beverley M Shields, Matthew J Simmonds, Debbie J Smyth, Elilan Somaskantharajah, Katarina Spanova, Sophia Steer, Jonathan Stephens, Helen E Stevens, Kathy Stirrups, Millicent A Stone, David P Strachan, Zhan Su, Deborah P M Symmons, John R Thompson, Wendy Thomson, Martin D Tobin, Mary E Travers, Clare Turnbull, Damjan Vukcevic, Louise V Wain, Mark Walker, Neil M Walker, Chris Wallace, Margaret Warren-Perry, Nicholas A Watkins, John Webster, Michael N Weedon, Anthony G Wilson, Matthew Woodburn, B Paul Wordsworth, Chris Yau, Allan H Young, Eleftheria Zeggini, Matthew A Brown, Paul R Burton, Mark J Caulfield, Alastair Compston, Martin Farrall, Stephen C L Gough, Alistair S Hall, Andrew T Hattersley, Adrian V S Hill, Christopher G Mathew, Marcus Pembrey, Jack Satsangi, Michael R Stratton, Jane Worthington, Matthew E Hurles, Audrey Duncanson, Willem H Ouwehand, Miles Parkes, Nazneen Rahman, John A Todd, Nilesh J Samani, Dominic P Kwiatkowski, Mark I McCarthy, Nick Craddock, Panos Deloukas, Peter Donnelly

Affiliation

¹ Department of Medical Genetics, Cambridge Institute for Medical Research, Juvenile Diabetes Research Foundation/ Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. jason.cooper@cimr.cam.ac.uk

PMID: 22922229
PMCID: PMC3490518
DOI: 10.1093/hmg/dds357

Seven newly identified loci for autoimmune thyroid disease

Jason D Cooper et al. Hum Mol Genet. 2012.

. 2012 Dec 1;21(23):5202-8.

doi: 10.1093/hmg/dds357. Epub 2012 Aug 24.

Authors

Collaborators

Wellcome Trust Case Control Consortium:
Jan Aerts, Tariq Ahmad, Hazel Arbury, Anthony Attwood, Adam Auton, Stephen G Ball, Anthony J Balmforth, Chris Barnes, Jeffrey C Barrett, Inês Barroso, Anne Barton, Amanda J Bennett, Sanjeev Bhaskar, Katarzyna Blaszczyk, John Bowes, Oliver J Brand, Peter S Braund, Francesca Bredin, Gerome Breen, Morris J Brown, Ian N Bruce, Jaswinder Bull, Oliver S Burren, John Burton, Jake Byrnes, Sian Caesar, Niall Cardin, Chris M Clee, Alison J Coffey, John M C Connell, Donald F Conrad, Jason D Cooper, Anna F Dominiczak, Kate Downes, Hazel E Drummond, Darshna Dudakia, Andrew Dunham, Bernadette Ebbs, Diana Eccles, Sarah Edkins, Cathryn Edwards, Anna Elliot, Paul Emery, David M Evans, Gareth Evans, Steve Eyre, Anne Farmer, I Nicol Ferrier, Edward Flynn, Alistair Forbes, Liz Forty, Jayne A Franklyn, Timothy M Frayling, Rachel M Freathy, Eleni Giannoulatou, Polly Gibbs, Paul Gilbert, Katherine Gordon-Smith, Emma Gray, Elaine Green, Chris J Groves, Detelina Grozeva, Rhian Gwilliam, Anita Hall, Naomi Hammond, Matt Hardy, Pile Harrison, Neelam Hassanali, Husam Hebaishi, Sarah Hines, Anne Hinks, Graham A Hitman, Lynne Hocking, Chris Holmes, Eleanor Howard, Philip Howard, Joanna M M Howson, Debbie Hughes, Sarah Hunt, John D Isaacs, Mahim Jain, Derek P Jewell, Toby Johnson, Jennifer D Jolley, Ian R Jones, Lisa A Jones, George Kirov, Cordelia F Langford, Hana Lango-Allen, G Mark Lathrop, James Lee, Kate L Lee, Charlie Lees, Kevin Lewis, Cecilia M Lindgren, Meeta Maisuria-Armer, Julian Maller, John Mansfield, Jonathan L Marchini, Paul Martin, Dunecan C O Massey, Wendy L McArdle, Peter McGuffin, Kirsten E McLay, Gil McVean, Alex Mentzer, Michael L Mimmack, Ann E Morgan, Andrew P Morris, Craig Mowat, Patricia B Munroe, Simon Myers, William Newman, Elaine R Nimmo, Michael C O'Donovan, Abiodun Onipinla, Nigel R Ovington, Michael J Owen, Kimmo Palin, Aarno Palotie, Kirstie Parnell, Richard Pearson, David Pernet, John R B Perry, Anne Phillips, Vincent Plagnol, Natalie J Prescott, Inga Prokopenko, Michael A Quail, Suzanne Rafelt, Nigel W Rayner, David M Reid, Anthony Renwick, Susan M Ring, Neil Robertson, Samuel Robson, Ellie Russell, David St Clair, Jennifer G Sambrook, Jeremy D Sanderson, Stephen J Sawcer, Helen Schuilenburg, Carol E Scott, Richard Scott, Sheila Seal, Sue Shaw-Hawkins, Beverley M Shields, Matthew J Simmonds, Debbie J Smyth, Elilan Somaskantharajah, Katarina Spanova, Sophia Steer, Jonathan Stephens, Helen E Stevens, Kathy Stirrups, Millicent A Stone, David P Strachan, Zhan Su, Deborah P M Symmons, John R Thompson, Wendy Thomson, Martin D Tobin, Mary E Travers, Clare Turnbull, Damjan Vukcevic, Louise V Wain, Mark Walker, Neil M Walker, Chris Wallace, Margaret Warren-Perry, Nicholas A Watkins, John Webster, Michael N Weedon, Anthony G Wilson, Matthew Woodburn, B Paul Wordsworth, Chris Yau, Allan H Young, Eleftheria Zeggini, Matthew A Brown, Paul R Burton, Mark J Caulfield, Alastair Compston, Martin Farrall, Stephen C L Gough, Alistair S Hall, Andrew T Hattersley, Adrian V S Hill, Christopher G Mathew, Marcus Pembrey, Jack Satsangi, Michael R Stratton, Jane Worthington, Matthew E Hurles, Audrey Duncanson, Willem H Ouwehand, Miles Parkes, Nazneen Rahman, John A Todd, Nilesh J Samani, Dominic P Kwiatkowski, Mark I McCarthy, Nick Craddock, Panos Deloukas, Peter Donnelly

Affiliation

¹ Department of Medical Genetics, Cambridge Institute for Medical Research, Juvenile Diabetes Research Foundation/ Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. jason.cooper@cimr.cam.ac.uk

PMID: 22922229
PMCID: PMC3490518
DOI: 10.1093/hmg/dds357

Abstract

Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

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References

1. Smyth D., Cooper J.D., Collins J.E., Heward J.M., Franklyn J.A., Howson J.M., Vella A., Nutland S., Rance H.E., Maier L., et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes. 2004;53:3020–3023. doi:10.2337/diabetes.53.11.3020. - DOI - PubMed
1. Ueda H., Howson J.M., Esposito L., Heward J., Snook H., Chamberlain G., Rainbow D.B., Hunter K.M., Smith A.N., Di Genova G., et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423:506–511. doi:10.1038/nature01621. - DOI - PubMed
1. Trynka G., Hunt K.A., Bockett N.A., Romanos J., Mistry V., Szperl A., Bakker S.F., Bardella M.T., Bhaw-Rosun L., Castillejo G., et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 2011;43:1193–1201. doi:10.1038/ng.998. - DOI - PMC - PubMed
1. McGrogan A., Seaman H.E., Wright J.W., de Vries C.S. The incidence of autoimmune thyroid disease: a systematic review of the literature. Clin. Endocrinol. (Oxf.) 2008;69:687–696. doi:10.1111/j.1365-2265.2008.03338.x. - DOI - PubMed
1. Chu X., Pan C.M., Zhao S.X., Liang J., Gao G.Q., Zhang X.M., Yuan G.Y., Li C.G., Xue L.Q., Shen M., et al. A genome-wide association study identifies two new risk loci for Graves’ disease. Nat. Genet. 2011;43:897–901. doi:10.1038/ng.898. - DOI - PubMed

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[1] Smyth D., Cooper J.D., Collins J.E., Heward J.M., Franklyn J.A., Howson J.M., Vella A., Nutland S., Rance H.E., Maier L., et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes. 2004;53:3020–3023. doi:10.2337/diabetes.53.11.3020. - DOI - PubMed

[2] Smyth D., Cooper J.D., Collins J.E., Heward J.M., Franklyn J.A., Howson J.M., Vella A., Nutland S., Rance H.E., Maier L., et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes. 2004;53:3020–3023. doi:10.2337/diabetes.53.11.3020. - DOI - PubMed

[3] Ueda H., Howson J.M., Esposito L., Heward J., Snook H., Chamberlain G., Rainbow D.B., Hunter K.M., Smith A.N., Di Genova G., et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423:506–511. doi:10.1038/nature01621. - DOI - PubMed

[4] Ueda H., Howson J.M., Esposito L., Heward J., Snook H., Chamberlain G., Rainbow D.B., Hunter K.M., Smith A.N., Di Genova G., et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003;423:506–511. doi:10.1038/nature01621. - DOI - PubMed

[5] Trynka G., Hunt K.A., Bockett N.A., Romanos J., Mistry V., Szperl A., Bakker S.F., Bardella M.T., Bhaw-Rosun L., Castillejo G., et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 2011;43:1193–1201. doi:10.1038/ng.998. - DOI - PMC - PubMed

[6] Trynka G., Hunt K.A., Bockett N.A., Romanos J., Mistry V., Szperl A., Bakker S.F., Bardella M.T., Bhaw-Rosun L., Castillejo G., et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 2011;43:1193–1201. doi:10.1038/ng.998. - DOI - PMC - PubMed

[7] McGrogan A., Seaman H.E., Wright J.W., de Vries C.S. The incidence of autoimmune thyroid disease: a systematic review of the literature. Clin. Endocrinol. (Oxf.) 2008;69:687–696. doi:10.1111/j.1365-2265.2008.03338.x. - DOI - PubMed

[8] McGrogan A., Seaman H.E., Wright J.W., de Vries C.S. The incidence of autoimmune thyroid disease: a systematic review of the literature. Clin. Endocrinol. (Oxf.) 2008;69:687–696. doi:10.1111/j.1365-2265.2008.03338.x. - DOI - PubMed

[9] Chu X., Pan C.M., Zhao S.X., Liang J., Gao G.Q., Zhang X.M., Yuan G.Y., Li C.G., Xue L.Q., Shen M., et al. A genome-wide association study identifies two new risk loci for Graves’ disease. Nat. Genet. 2011;43:897–901. doi:10.1038/ng.898. - DOI - PubMed

[10] Chu X., Pan C.M., Zhao S.X., Liang J., Gao G.Q., Zhang X.M., Yuan G.Y., Li C.G., Xue L.Q., Shen M., et al. A genome-wide association study identifies two new risk loci for Graves’ disease. Nat. Genet. 2011;43:897–901. doi:10.1038/ng.898. - DOI - PubMed

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Seven newly identified loci for autoimmune thyroid disease

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Seven newly identified loci for autoimmune thyroid disease

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