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 & 13 others 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

Research output: Contribution to journalArticle

539 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)776-782
Number of pages7
JournalNature Genetics
Volume41
Issue number7
DOIs
StatePublished - Jul 1 2009

Fingerprint

Multiple Sclerosis
Meta-Analysis
Genome
Alleles
Odds Ratio
Interferon Type I
Genome-Wide Association Study
Gene Frequency
Interferons
Transcription Factors
Messenger RNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

De Jager, P. L., Jia, X., Wang, J., De Bakker, P. I. W., Ottoboni, L., Aggarwal, N. T., ... 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

Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. / De Jager, Philip L.; Jia, Xiaoming; Wang, Joanne; De Bakker, Paul I W; Ottoboni, Linda; Aggarwal, Neelum T.; Piccio, Laura; Raychaudhuri, Soumya; Tran, Dong; Aubin, Cristin; Briskin, Rebeccah; Romano, Susan; Baranzini, Sergio E.; McCauley, Jacob L; Pericak-Vance, Margaret A; Haines, Jonathan L.; Gibson, Rachel A.; Naeglin, Yvonne; Uitdehaag, Bernard; Matthews, Paul M.; Kappos, Ludwig; Polman, Chris; McArdle, Wendy L.; Strachan, David P.; Evans, Denis; Cross, Anne H.; Daly, Mark J.; Compston, Alastair; Sawcer, Stephen J.; Weiner, Howard L.; Hauser, Stephen L.; Hafler, David A.; Oksenberg, Jorge R.

In: Nature Genetics, Vol. 41, No. 7, 01.07.2009, p. 776-782.

Research output: Contribution to journalArticle

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
De Jager, Philip L. ; Jia, Xiaoming ; Wang, Joanne ; De Bakker, Paul I W ; Ottoboni, Linda ; Aggarwal, Neelum T. ; Piccio, Laura ; Raychaudhuri, Soumya ; Tran, Dong ; Aubin, Cristin ; Briskin, Rebeccah ; Romano, Susan ; Baranzini, Sergio E. ; McCauley, Jacob L ; Pericak-Vance, Margaret A ; Haines, Jonathan L. ; Gibson, Rachel A. ; Naeglin, Yvonne ; Uitdehaag, Bernard ; Matthews, Paul M. ; Kappos, Ludwig ; Polman, Chris ; McArdle, Wendy L. ; Strachan, David P. ; Evans, Denis ; Cross, Anne H. ; Daly, Mark J. ; Compston, Alastair ; Sawcer, Stephen J. ; Weiner, Howard L. ; Hauser, Stephen L. ; Hafler, David A. ; Oksenberg, Jorge R. / Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. In: Nature Genetics. 2009 ; Vol. 41, No. 7. pp. 776-782.
@article{467903d49dd6445bb76959c039ff67dc,
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.",
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.}",
year = "2009",
month = "7",
day = "1",
doi = "10.1038/ng.401",
language = "English",
volume = "41",
pages = "776--782",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",

}

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.

PY - 2009/7/1

Y1 - 2009/7/1

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=67649876123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649876123&partnerID=8YFLogxK

U2 - 10.1038/ng.401

DO - 10.1038/ng.401

M3 - Article

VL - 41

SP - 776

EP - 782

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -