Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

Melanie Bahlo, David R. Booth, Simon Broadley, Matthew A. Brown, Simon J. Foote, Lyn R. Griffiths, Trevor J. Kilpatrick, Jeanette Lechner-Scott, Pablo Moscato, Victoria M. Perreau, Justin P. Rubio, Rodney J. Scott, Jim Stankovich, Graeme J. Stewart, Bruce V. Taylor, James Wiley, Glynnis Clarke, Mathew B. Cox, Peter A. Csurhes, Patrick Danoy & 29 others Karen Drysdale, Judith Field, Judith M. Greer, Preethi Guru, Johanna Hadler, Brendan J. McMorran, Cathy J. Jensen, Laura J. Johnson, Ruth McCallum, Marilyn Merriman, Tony Merriman, Karen Pryce, Lotfi Tajouri, Ella J. Wilkins, Brian L. Browning, Devindri Perera, Devindri Perera, Simon Broadley, Helmut Butzkueven, William M. Carroll, Caron Chapman, Allan G. Kermode, Mark Marriott, Deborah Mason, Robert N. Heard, Michael P. Pender, Mark Slee, Niall Tubridy, Ernest Willoughby

Research output: Contribution to journalLetterResearchpeer-review

399 Citations (Scopus)

Abstract

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 × 10 11; rs10876994, P = 2.7 × 10 10; rs12368653, P = 1.0 × 10 7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 × 10 7; rs1569723, P = 2.9 × 10 7). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 × 10 184; CD58, P = 9.6 × 10 8; EVI5-RPL5, P = 2.5 × 10 6; IL2RA, P = 7.4 × 10 6; CLEC16A, P = 1.1 × 10 4; IL7R, P = 1.3 × 10 3; TYK2, P = 3.5 × 10 3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Original languageEnglish
Pages (from-to)824-828
Number of pages5
JournalNature Genetics
Volume41
Issue number7
DOIs
Publication statusPublished - 1 Jul 2009
Externally publishedYes

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Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 12
Genome-Wide Association Study
Multiple Sclerosis
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 14
Autoimmune Diseases
Chromosomes
HLA-DR15 antigen

Cite this

Bahlo, M., Booth, D. R., Broadley, S., Brown, M. A., Foote, S. J., Griffiths, L. R., ... Willoughby, E. (2009). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nature Genetics, 41(7), 824-828. https://doi.org/10.1038/ng.396
Bahlo, Melanie ; Booth, David R. ; Broadley, Simon ; Brown, Matthew A. ; Foote, Simon J. ; Griffiths, Lyn R. ; Kilpatrick, Trevor J. ; Lechner-Scott, Jeanette ; Moscato, Pablo ; Perreau, Victoria M. ; Rubio, Justin P. ; Scott, Rodney J. ; Stankovich, Jim ; Stewart, Graeme J. ; Taylor, Bruce V. ; Wiley, James ; Clarke, Glynnis ; Cox, Mathew B. ; Csurhes, Peter A. ; Danoy, Patrick ; Drysdale, Karen ; Field, Judith ; Greer, Judith M. ; Guru, Preethi ; Hadler, Johanna ; McMorran, Brendan J. ; Jensen, Cathy J. ; Johnson, Laura J. ; McCallum, Ruth ; Merriman, Marilyn ; Merriman, Tony ; Pryce, Karen ; Tajouri, Lotfi ; Wilkins, Ella J. ; Browning, Brian L. ; Perera, Devindri ; Perera, Devindri ; Broadley, Simon ; Butzkueven, Helmut ; Carroll, William M. ; Chapman, Caron ; Kermode, Allan G. ; Marriott, Mark ; Mason, Deborah ; Heard, Robert N. ; Pender, Michael P. ; Slee, Mark ; Tubridy, Niall ; Willoughby, Ernest. / Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. In: Nature Genetics. 2009 ; Vol. 41, No. 7. pp. 824-828.
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title = "Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20",
abstract = "To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 × 10 11; rs10876994, P = 2.7 × 10 10; rs12368653, P = 1.0 × 10 7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 × 10 7; rs1569723, P = 2.9 × 10 7). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 × 10 184; CD58, P = 9.6 × 10 8; EVI5-RPL5, P = 2.5 × 10 6; IL2RA, P = 7.4 × 10 6; CLEC16A, P = 1.1 × 10 4; IL7R, P = 1.3 × 10 3; TYK2, P = 3.5 × 10 3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).",
author = "Melanie Bahlo and Booth, {David R.} and Simon Broadley and Brown, {Matthew A.} and Foote, {Simon J.} and Griffiths, {Lyn R.} and Kilpatrick, {Trevor J.} and Jeanette Lechner-Scott and Pablo Moscato and Perreau, {Victoria M.} and Rubio, {Justin P.} and Scott, {Rodney J.} and Jim Stankovich and Stewart, {Graeme J.} and Taylor, {Bruce V.} and James Wiley and Glynnis Clarke and Cox, {Mathew B.} and Csurhes, {Peter A.} and Patrick Danoy and Karen Drysdale and Judith Field and Greer, {Judith M.} and Preethi Guru and Johanna Hadler and McMorran, {Brendan J.} and Jensen, {Cathy J.} and Johnson, {Laura J.} and Ruth McCallum and Marilyn Merriman and Tony Merriman and Karen Pryce and Lotfi Tajouri and Wilkins, {Ella J.} and Browning, {Brian L.} and Devindri Perera and Devindri Perera and Simon Broadley and Helmut Butzkueven and Carroll, {William M.} and Caron Chapman and Kermode, {Allan G.} and Mark Marriott and Deborah Mason and Heard, {Robert N.} and Pender, {Michael P.} and Mark Slee and Niall Tubridy and Ernest Willoughby",
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Bahlo, M, Booth, DR, Broadley, S, Brown, MA, Foote, SJ, Griffiths, LR, Kilpatrick, TJ, Lechner-Scott, J, Moscato, P, Perreau, VM, Rubio, JP, Scott, RJ, Stankovich, J, Stewart, GJ, Taylor, BV, Wiley, J, Clarke, G, Cox, MB, Csurhes, PA, Danoy, P, Drysdale, K, Field, J, Greer, JM, Guru, P, Hadler, J, McMorran, BJ, Jensen, CJ, Johnson, LJ, McCallum, R, Merriman, M, Merriman, T, Pryce, K, Tajouri, L, Wilkins, EJ, Browning, BL, Perera, D, Perera, D, Broadley, S, Butzkueven, H, Carroll, WM, Chapman, C, Kermode, AG, Marriott, M, Mason, D, Heard, RN, Pender, MP, Slee, M, Tubridy, N & Willoughby, E 2009, 'Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20' Nature Genetics, vol. 41, no. 7, pp. 824-828. https://doi.org/10.1038/ng.396

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. / Bahlo, Melanie; Booth, David R.; Broadley, Simon; Brown, Matthew A.; Foote, Simon J.; Griffiths, Lyn R.; Kilpatrick, Trevor J.; Lechner-Scott, Jeanette; Moscato, Pablo; Perreau, Victoria M.; Rubio, Justin P.; Scott, Rodney J.; Stankovich, Jim; Stewart, Graeme J.; Taylor, Bruce V.; Wiley, James; Clarke, Glynnis; Cox, Mathew B.; Csurhes, Peter A.; Danoy, Patrick; Drysdale, Karen; Field, Judith; Greer, Judith M.; Guru, Preethi; Hadler, Johanna; McMorran, Brendan J.; Jensen, Cathy J.; Johnson, Laura J.; McCallum, Ruth; Merriman, Marilyn; Merriman, Tony; Pryce, Karen; Tajouri, Lotfi; Wilkins, Ella J.; Browning, Brian L.; Perera, Devindri; Perera, Devindri; Broadley, Simon; Butzkueven, Helmut; Carroll, William M.; Chapman, Caron; Kermode, Allan G.; Marriott, Mark; Mason, Deborah; Heard, Robert N.; Pender, Michael P.; Slee, Mark; Tubridy, Niall; Willoughby, Ernest.

In: Nature Genetics, Vol. 41, No. 7, 01.07.2009, p. 824-828.

Research output: Contribution to journalLetterResearchpeer-review

TY - JOUR

T1 - Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

AU - Bahlo, Melanie

AU - Booth, David R.

AU - Broadley, Simon

AU - Brown, Matthew A.

AU - Foote, Simon J.

AU - Griffiths, Lyn R.

AU - Kilpatrick, Trevor J.

AU - Lechner-Scott, Jeanette

AU - Moscato, Pablo

AU - Perreau, Victoria M.

AU - Rubio, Justin P.

AU - Scott, Rodney J.

AU - Stankovich, Jim

AU - Stewart, Graeme J.

AU - Taylor, Bruce V.

AU - Wiley, James

AU - Clarke, Glynnis

AU - Cox, Mathew B.

AU - Csurhes, Peter A.

AU - Danoy, Patrick

AU - Drysdale, Karen

AU - Field, Judith

AU - Greer, Judith M.

AU - Guru, Preethi

AU - Hadler, Johanna

AU - McMorran, Brendan J.

AU - Jensen, Cathy J.

AU - Johnson, Laura J.

AU - McCallum, Ruth

AU - Merriman, Marilyn

AU - Merriman, Tony

AU - Pryce, Karen

AU - Tajouri, Lotfi

AU - Wilkins, Ella J.

AU - Browning, Brian L.

AU - Perera, Devindri

AU - Perera, Devindri

AU - Broadley, Simon

AU - Butzkueven, Helmut

AU - Carroll, William M.

AU - Chapman, Caron

AU - Kermode, Allan G.

AU - Marriott, Mark

AU - Mason, Deborah

AU - Heard, Robert N.

AU - Pender, Michael P.

AU - Slee, Mark

AU - Tubridy, Niall

AU - Willoughby, Ernest

PY - 2009/7/1

Y1 - 2009/7/1

N2 - To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 × 10 11; rs10876994, P = 2.7 × 10 10; rs12368653, P = 1.0 × 10 7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 × 10 7; rs1569723, P = 2.9 × 10 7). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 × 10 184; CD58, P = 9.6 × 10 8; EVI5-RPL5, P = 2.5 × 10 6; IL2RA, P = 7.4 × 10 6; CLEC16A, P = 1.1 × 10 4; IL7R, P = 1.3 × 10 3; TYK2, P = 3.5 × 10 3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

AB - To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 × 10 11; rs10876994, P = 2.7 × 10 10; rs12368653, P = 1.0 × 10 7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 × 10 7; rs1569723, P = 2.9 × 10 7). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 × 10 184; CD58, P = 9.6 × 10 8; EVI5-RPL5, P = 2.5 × 10 6; IL2RA, P = 7.4 × 10 6; CLEC16A, P = 1.1 × 10 4; IL7R, P = 1.3 × 10 3; TYK2, P = 3.5 × 10 3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

UR - http://www.scopus.com/inward/record.url?scp=67649881102&partnerID=8YFLogxK

U2 - 10.1038/ng.396

DO - 10.1038/ng.396

M3 - Letter

VL - 41

SP - 824

EP - 828

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -