Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci

Philip L. De Jager; Xiaoming Jia; Joanne Wang; Paul I W De Bakker; Linda Ottoboni; Neelum T. Aggarwal; Laura Piccio; Soumya Raychaudhuri; Dong Tran; Cristin Aubin; Rebeccah Briskin; Susan Romano; Sergio E. Baranzini; Jacob L. McCauley; Margaret A. Pericak-Vance; Jonathan L. Haines; Rachel A. Gibson; Yvonne Naeglin; Bernard Uitdehaag; Paul M. Matthews; Ludwig Kappos; Chris Polman; Wendy L. McArdle; David P. Strachan; Denis Evans; Anne H. Cross; Mark J. Daly; Alastair Compston; Stephen J. Sawcer; Howard L. Weiner; Stephen L. Hauser; David A. Hafler; Jorge R. Oksenberg

doi:10.1038/ng.401

Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci

Philip L. De Jager, Xiaoming Jia, Joanne Wang, Paul I W De Bakker, Linda Ottoboni, Neelum T. Aggarwal, Laura Piccio, Soumya Raychaudhuri, Dong Tran, Cristin Aubin, Rebeccah Briskin, Susan Romano, Sergio E. Baranzini, Jacob L. McCauley, Margaret A. Pericak-Vance, Jonathan L. Haines, Rachel A. Gibson, Yvonne Naeglin, Bernard Uitdehaag, Paul M. MatthewsLudwig Kappos, Chris Polman, Wendy L. McArdle, David P. Strachan, Denis Evans, Anne H. Cross, Mark J. Daly, Alastair Compston, Stephen J. Sawcer, Howard L. Weiner, Stephen L. Hauser, David A. Hafler, Jorge R. Oksenberg

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

Abstract

We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 × 10 11), IRF8 (P = 3.73 × 10 9) and CD6 (P = 3.79 × 10 9). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio = 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency = 0.02; odds ratio = 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS. © 2009 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	776-782
Number of pages	6
Journal	Nature Genetics
Volume	41
Issue number	7
DOIs	https://doi.org/10.1038/ng.401
Publication status	Published - Jul 2009

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De Jager, P. L., Jia, X., Wang, J., De Bakker, P. I. W., Ottoboni, L., Aggarwal, N. T., Piccio, L., Raychaudhuri, S., Tran, D., Aubin, C., Briskin, R., Romano, S., Baranzini, S. E., McCauley, J. L., Pericak-Vance, M. A., Haines, J. L., Gibson, R. A., Naeglin, Y., Uitdehaag, B., ... Oksenberg, J. R. (2009). Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nature Genetics, 41(7), 776-782. https://doi.org/10.1038/ng.401

@article{7b26cddb274d4dd9848c146756a20106,

title = "Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci",

abstract = "We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 × 10 11), IRF8 (P = 3.73 × 10 9) and CD6 (P = 3.79 × 10 9). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio = 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency = 0.02; odds ratio = 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS. {\textcopyright} 2009 Nature America, Inc. All rights reserved.",

author = "{De Jager}, {Philip L.} and Xiaoming Jia and Joanne Wang and {De Bakker}, {Paul I W} and Linda Ottoboni and Aggarwal, {Neelum T.} and Laura Piccio and Soumya Raychaudhuri and Dong Tran and Cristin Aubin and Rebeccah Briskin and Susan Romano and Baranzini, {Sergio E.} and McCauley, {Jacob L.} and Pericak-Vance, {Margaret A.} and Haines, {Jonathan L.} and Gibson, {Rachel A.} and Yvonne Naeglin and Bernard Uitdehaag and Matthews, {Paul M.} and Ludwig Kappos and Chris Polman and McArdle, {Wendy L.} and Strachan, {David P.} and Denis Evans and Cross, {Anne H.} and Daly, {Mark J.} and Alastair Compston and Sawcer, {Stephen J.} and Weiner, {Howard L.} and Hauser, {Stephen L.} and Hafler, {David A.} and Oksenberg, {Jorge R.}",

note = "068545/Z/02, Wellcome Trust, United KingdomG0000934, Medical Research Council, United KingdomK08 AR055688-01A1, NIAMS NIH HHS, United StatesK08 NS46341, NINDS NIH HHS, United StatesP01 AI039671, NIAID NIH HHS, United StatesR01 NS046630, NINDS NIH HHS, United StatesR01 NS049477, NINDS NIH HHS, United States",

year = "2009",

month = jul,

doi = "10.1038/ng.401",

language = "English",

volume = "41",

pages = "776--782",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "7",

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De Jager, PL, Jia, X, Wang, J, De Bakker, PIW, Ottoboni, L, Aggarwal, NT, Piccio, L, Raychaudhuri, S, Tran, D, Aubin, C, Briskin, R, Romano, S, Baranzini, SE, McCauley, JL, Pericak-Vance, MA, Haines, JL, Gibson, RA, Naeglin, Y, Uitdehaag, B, Matthews, PM, Kappos, L, Polman, C, McArdle, WL, Strachan, DP, Evans, D, Cross, AH, Daly, MJ, Compston, A, Sawcer, SJ, Weiner, HL, Hauser, SL, Hafler, DA & Oksenberg, JR 2009, 'Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci', Nature Genetics, vol. 41, no. 7, pp. 776-782. https://doi.org/10.1038/ng.401

TY - JOUR

T1 - Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci

AU - De Jager, Philip L.

AU - Jia, Xiaoming

AU - Wang, Joanne

AU - De Bakker, Paul I W

AU - Ottoboni, Linda

AU - Aggarwal, Neelum T.

AU - Piccio, Laura

AU - Raychaudhuri, Soumya

AU - Tran, Dong

AU - Aubin, Cristin

AU - Briskin, Rebeccah

AU - Romano, Susan

AU - Baranzini, Sergio E.

AU - McCauley, Jacob L.

AU - Pericak-Vance, Margaret A.

AU - Haines, Jonathan L.

AU - Gibson, Rachel A.

AU - Naeglin, Yvonne

AU - Uitdehaag, Bernard

AU - Matthews, Paul M.

AU - Kappos, Ludwig

AU - Polman, Chris

AU - McArdle, Wendy L.

AU - Strachan, David P.

AU - Evans, Denis

AU - Cross, Anne H.

AU - Daly, Mark J.

AU - Compston, Alastair

AU - Sawcer, Stephen J.

AU - Weiner, Howard L.

AU - Hauser, Stephen L.

AU - Hafler, David A.

AU - Oksenberg, Jorge R.

N1 - 068545/Z/02, Wellcome Trust, United KingdomG0000934, Medical Research Council, United KingdomK08 AR055688-01A1, NIAMS NIH HHS, United StatesK08 NS46341, NINDS NIH HHS, United StatesP01 AI039671, NIAID NIH HHS, United StatesR01 NS046630, NINDS NIH HHS, United StatesR01 NS049477, NINDS NIH HHS, United States

PY - 2009/7

Y1 - 2009/7

N2 - We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 × 10 11), IRF8 (P = 3.73 × 10 9) and CD6 (P = 3.79 × 10 9). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio = 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency = 0.02; odds ratio = 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS. © 2009 Nature America, Inc. All rights reserved.

AB - We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 × 10 11), IRF8 (P = 3.73 × 10 9) and CD6 (P = 3.79 × 10 9). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio = 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency = 0.02; odds ratio = 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS. © 2009 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.401

DO - 10.1038/ng.401

M3 - Article

C2 - 19525953

SN - 1061-4036

VL - 41

SP - 776

EP - 782

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci

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