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

Melanie Bahlo; David R. Booth; Simon A. 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; 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; Sharon R. Browning; Devindri Perera; 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

doi:10.1038/ng.396

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

Melanie Bahlo, David R. Booth, Simon A. 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 DanoyKaren 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, Sharon R. Browning, Devindri Perera, 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	824-828
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	7
DOIs	https://doi.org/10.1038/ng.396
Publication status	Published - Jul 2009
Externally published	Yes

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Bahlo, M., Booth, D. R., Broadley, S. A., Brown, M. A., Foote, S. J., Griffiths, L. R., Kilpatrick, T. J., Lechner-Scott, J., Moscato, P., Perreau, V. M., Rubio, J. P., Scott, R. J., Stankovich, J., Stewart, G. J., Taylor, B. V., Wiley, J., Clarke, G., Cox, M. B., Csurhes, P. A., ... 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

@article{d87bd5e8e1104579ab428da15c2d0778,

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 Broadley, {Simon A.} 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 Browning, {Sharon R.} and Devindri Perera 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",

year = "2009",

month = jul,

doi = "10.1038/ng.396",

language = "English",

volume = "41",

pages = "824--828",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "7",

}

Bahlo, M, Booth, DR, Broadley, SA, 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, Browning, SR, Perera, D, 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

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 A.

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 - Browning, Sharon R.

AU - Perera, Devindri

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

Y1 - 2009/7

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).

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U2 - 10.1038/ng.396

DO - 10.1038/ng.396

M3 - Article

SN - 1061-4036

VL - 41

SP - 824

EP - 828

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

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

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