Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

被引：1106

作者：

Newport, Melanie

Sirugo, Giorgio

Lyons, Emily

Vannberg, Fredrik

Hill, Adrian V. S.

Bradbury, Linda A.

Farrar, Claire

Pointon, Jennifer J.

Wordsworth, Paul

Brown, Matthew A.

Franklyn, Jayne A.

Heward, Joanne M.

Simmonds, Matthew J.

Gough, Stephen C. L.

Seal, Sheila

Stratton, Michael R.

Rahman, Nazneen

Ban, Maria

Goris, An

Sawcer, Stephen J.

Compston, Alastair

Conway, David

Jallow, Muminatou

Newport, Melanie

Sirugo, Giorgio

Rockett, Kirk A.

Kwiatkowski, Dominic P.

Bumpstead, Suzannah J.

Chaney, Amy

Downes, Kate

Ghori, Mohammed J. R.

Gwilliam, Rhian

Hunt, Sarah E.

Inouye, Michael

Keniry, Andrew

King, Emma

McGinnis, Ralph

Potter, Simon

Ravindrarajah, Rathi

Whittaker, Pamela

Widden, Claire

Withers, David

Deloukas, Panos

Leung, Hin-Tak

Nutland, Sarah

Stevens, Helen E.

Walker, Neil M.

Todd, John A.

Easton, Doug

Clayton, David G.

机构：

[1] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester LE1 7RH, Leics, England

[2] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Juvenile Diabet Res Fdn Wellcome Trust Diabet & I, Cambridge CB2 0XY, England

[3] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[4] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, Wales

[5] Wellcome Trust Res Labs, London NW1 2BE, England

[6] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[7] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LJ, England

[8] Univ Cambridge, Dept Haematol, Cambridge CB2 2PT, England

[9] Cambridge Ctr, Natl Hlth Serv Blood & Transplant, Cambridge CB2 2PT, England

[10] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England

[11] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[12] Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England

[13] Natl Hlth Serv Blood & Transplant, Sheffield Ctr, Sheffield S5 7JN, S Yorkshire, England

[14] Natl Hlth Serv Blood & Transplant, Brentwood Ctr, Brentwood CM15 8DP, Essex, England

[15] Scottish Natl Blood Transfus Serv, Edinburgh CB17 7QT, Midlothian, Scotland

[16] Natl Hlth Serv Blood & Transplant, Southampton Ctr, Southampton SO16 5AF, Hants, England

[17] Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol BS8 1TQ, Avon, England

[18] St Georges Univ London, Div Community Hlth Serv, London SW17 0RE, England

[19] UCL, Inst Child Hlth, London WC1N 1EH, England

[20] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland

[21] Univ Birmingham, Div Neurosci, Dept Psychiat, Birmingham B15 2QZ, W Midlands, England

[22] Cardiff Univ, Sch Med, Dept Med Psychol, Cardiff CF14 4XN, Wales

[23] Kings Coll London, Inst Psychiat, SGDP, London SE5 8AF, England

[24] Royal Victoria Infirm, Sch Neurol Neurobiol & Psychiat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[25] Univ Leeds, Fac Med & Hlth, LIGHT & LIMM Res Inst, Leeds LS1 3EX, W Yorkshire, England

[26] Univ Cambridge, Addenbrookes Hosp, IBD Res Grp, Cambridge CB2 2QQ, England

[27] Univ Edinburgh, Western Gen Hosp, Sch Mol & Clin Med, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[28] Kings Coll London, Sch Med, Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England

[29] UCL, Hosp Trust, Inst Digest Dis, London NW1 2BU, England

[30] Guys & St Thomas NHS Fdn Trust, Dept Gastroenterol, London SE1 7EH, England

[31] Newcastle Univ, Royal Victoria Infirm, Dept Gastroenterol & Hepatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[32] Univ Oxford, Radcliffe Infirm, Gastroenterol Unit, Oxford OX2 6HE, England

[33] Aberdeen Royal Infirm, Aberdeen AB9 2ZB, Scotland

[34] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England

[35] Univ Cambridge, Addenbrookes Hosp, Diabet & Inflammat Lab, Cambridge CB2 2QQ, England

[36] Ctr Natl Genotypage, F-91057 Paris, France

[37] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland

[38] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London EC1M 6BQ, England

[39] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[40] Univ Manchester, Arc Epidemiol Res Unit, Manchester M13 9PT, Lancs, England

[41] Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 2QQ, England

[42] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England

[43] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DU, Devon, England

[44] Barts & London Royal London Hosp, Ctr Diabet & Metab Med, London E1 1BB, England

[45] Univ Newcastle, Sch Clin Med Sci, Diabet Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[46] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS2 8PR, Avon, England

[47] MRC Labs, Fajara, Gambia

[48] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst Canc Immunol & Metab Med, Woolloongabba, Qld 4102, Australia

[49] Univ Oxford, Botnar Res Ctr, Oxford OX3 7BN, England

[50] Univ Birmingham, Biomed Res Inst, Div Med Sci, Dept Med, Birmingham B15 2TT, W Midlands, England

来源：

NATURE GENETICS | 2007年 / 39卷 / 11期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.2007.17

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS), autoimmune thyroid disease (AITD), multiple sclerosis ( MS) and breast cancer ( BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major `seronegative' diseases.

引用

页码：1329 / 1337

页数：9

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