Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Maurizio A. Leone, Nadia Barizzone, Federica Esposito, Ausiliatrice Lucenti, Hanne F. Harbo, An Goris, Ingrid Kockum, Annette Bang Oturai, Elisabeth Gulowsen Celius, Inger L. Mero, Bénédicte Dubois, Tomas Olsson, Helle Bach Søndergaard, Daniele Cusi, Sara Lupoli, Bettina Kulle Andreassen, L. Barcellos, D. Booth, M. Comabella, A. Compston & 54 others S. D'Alfonso, P. De Jager, B. Fontaine, A. Goris, D. Hafler, J. Haines, H. F. Harbo, S. L. Hauser, C. Hawkins, B. Hemmer, J. Hillert, A. Ivinson, Jacob L McCauley, R. Martin, F. Martinelli Boneschi, J. L. McCauley, Margaret A Pericak-Vance, T. Olsson, A. Oturai, N. Patsopoulos, M. Pericak-Vance, J. Saarela, S. Sawcer, A. Spurkland, G. Stewart, F. Zipp, Kjell Morten Myhr, Franca R. Guerini, Paola Naldi, Daniela Galimberti, Elio Scarpini, Roberto Bergamaschi, Antonella Di Sapio, Domenico Caputo, Gabriella Rosso, Susanna Cordera, Paola Cavalla, Roberto Cavallo, Maria D. Benedetti, Marco Salvetti, Ruggero Capra, Angelo Ghezzi, Pietro Annovazzi, Gabriella Coniglio, Giuseppe Liberatore, Mariaemma Rodegher, Lucia Moiola, Bruno Colombo, Marta Radaelli, Paolo Rossi, Vittorio Martinelli, Giancarlo Comi, Filippo Martinelli-Boneschi, Sandra D'Alfonso

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB.

Original languageEnglish
Article numbere64408
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 13 2013
Externally publishedYes

Fingerprint

Oligoclonal Bands
sclerosis
Genetic Markers
Multiple Sclerosis
Cerebrospinal Fluid
genetic markers
Fluids
Single Nucleotide Polymorphism
Genome-Wide Association Study
Genes
odds ratio
HLA-DRB1 Chains
Odds Ratio
meta-analysis
HLA-A Antigens
Chromosomes
fluids
Computer Simulation
chromosomes
Meta-Analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Leone, M. A., Barizzone, N., Esposito, F., Lucenti, A., Harbo, H. F., Goris, A., ... D'Alfonso, S. (2013). Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients. PLoS One, 8(6), [e64408]. https://doi.org/10.1371/journal.pone.0064408

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients. / Leone, Maurizio A.; Barizzone, Nadia; Esposito, Federica; Lucenti, Ausiliatrice; Harbo, Hanne F.; Goris, An; Kockum, Ingrid; Oturai, Annette Bang; Celius, Elisabeth Gulowsen; Mero, Inger L.; Dubois, Bénédicte; Olsson, Tomas; Søndergaard, Helle Bach; Cusi, Daniele; Lupoli, Sara; Andreassen, Bettina Kulle; Barcellos, L.; Booth, D.; Comabella, M.; Compston, A.; D'Alfonso, S.; De Jager, P.; Fontaine, B.; Goris, A.; Hafler, D.; Haines, J.; Harbo, H. F.; Hauser, S. L.; Hawkins, C.; Hemmer, B.; Hillert, J.; Ivinson, A.; McCauley, Jacob L; Martin, R.; Martinelli Boneschi, F.; McCauley, J. L.; Pericak-Vance, Margaret A; Olsson, T.; Oturai, A.; Patsopoulos, N.; Pericak-Vance, M.; Saarela, J.; Sawcer, S.; Spurkland, A.; Stewart, G.; Zipp, F.; Myhr, Kjell Morten; Guerini, Franca R.; Naldi, Paola; Galimberti, Daniela; Scarpini, Elio; Bergamaschi, Roberto; Di Sapio, Antonella; Caputo, Domenico; Rosso, Gabriella; Cordera, Susanna; Cavalla, Paola; Cavallo, Roberto; Benedetti, Maria D.; Salvetti, Marco; Capra, Ruggero; Ghezzi, Angelo; Annovazzi, Pietro; Coniglio, Gabriella; Liberatore, Giuseppe; Rodegher, Mariaemma; Moiola, Lucia; Colombo, Bruno; Radaelli, Marta; Rossi, Paolo; Martinelli, Vittorio; Comi, Giancarlo; Martinelli-Boneschi, Filippo; D'Alfonso, Sandra.

In: PLoS One, Vol. 8, No. 6, e64408, 13.06.2013.

Research output: Contribution to journalArticle

Leone, MA, Barizzone, N, Esposito, F, Lucenti, A, Harbo, HF, Goris, A, Kockum, I, Oturai, AB, Celius, EG, Mero, IL, Dubois, B, Olsson, T, Søndergaard, HB, Cusi, D, Lupoli, S, Andreassen, BK, Barcellos, L, Booth, D, Comabella, M, Compston, A, D'Alfonso, S, De Jager, P, Fontaine, B, Goris, A, Hafler, D, Haines, J, Harbo, HF, Hauser, SL, Hawkins, C, Hemmer, B, Hillert, J, Ivinson, A, McCauley, JL, Martin, R, Martinelli Boneschi, F, McCauley, JL, Pericak-Vance, MA, Olsson, T, Oturai, A, Patsopoulos, N, Pericak-Vance, M, Saarela, J, Sawcer, S, Spurkland, A, Stewart, G, Zipp, F, Myhr, KM, Guerini, FR, Naldi, P, Galimberti, D, Scarpini, E, Bergamaschi, R, Di Sapio, A, Caputo, D, Rosso, G, Cordera, S, Cavalla, P, Cavallo, R, Benedetti, MD, Salvetti, M, Capra, R, Ghezzi, A, Annovazzi, P, Coniglio, G, Liberatore, G, Rodegher, M, Moiola, L, Colombo, B, Radaelli, M, Rossi, P, Martinelli, V, Comi, G, Martinelli-Boneschi, F & D'Alfonso, S 2013, 'Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients', PLoS One, vol. 8, no. 6, e64408. https://doi.org/10.1371/journal.pone.0064408
Leone MA, Barizzone N, Esposito F, Lucenti A, Harbo HF, Goris A et al. Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients. PLoS One. 2013 Jun 13;8(6). e64408. https://doi.org/10.1371/journal.pone.0064408
Leone, Maurizio A. ; Barizzone, Nadia ; Esposito, Federica ; Lucenti, Ausiliatrice ; Harbo, Hanne F. ; Goris, An ; Kockum, Ingrid ; Oturai, Annette Bang ; Celius, Elisabeth Gulowsen ; Mero, Inger L. ; Dubois, Bénédicte ; Olsson, Tomas ; Søndergaard, Helle Bach ; Cusi, Daniele ; Lupoli, Sara ; Andreassen, Bettina Kulle ; Barcellos, L. ; Booth, D. ; Comabella, M. ; Compston, A. ; D'Alfonso, S. ; De Jager, P. ; Fontaine, B. ; Goris, A. ; Hafler, D. ; Haines, J. ; Harbo, H. F. ; Hauser, S. L. ; Hawkins, C. ; Hemmer, B. ; Hillert, J. ; Ivinson, A. ; McCauley, Jacob L ; Martin, R. ; Martinelli Boneschi, F. ; McCauley, J. L. ; Pericak-Vance, Margaret A ; Olsson, T. ; Oturai, A. ; Patsopoulos, N. ; Pericak-Vance, M. ; Saarela, J. ; Sawcer, S. ; Spurkland, A. ; Stewart, G. ; Zipp, F. ; Myhr, Kjell Morten ; Guerini, Franca R. ; Naldi, Paola ; Galimberti, Daniela ; Scarpini, Elio ; Bergamaschi, Roberto ; Di Sapio, Antonella ; Caputo, Domenico ; Rosso, Gabriella ; Cordera, Susanna ; Cavalla, Paola ; Cavallo, Roberto ; Benedetti, Maria D. ; Salvetti, Marco ; Capra, Ruggero ; Ghezzi, Angelo ; Annovazzi, Pietro ; Coniglio, Gabriella ; Liberatore, Giuseppe ; Rodegher, Mariaemma ; Moiola, Lucia ; Colombo, Bruno ; Radaelli, Marta ; Rossi, Paolo ; Martinelli, Vittorio ; Comi, Giancarlo ; Martinelli-Boneschi, Filippo ; D'Alfonso, Sandra. / Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients. In: PLoS One. 2013 ; Vol. 8, No. 6.
@article{66818384dfed4ab5a98ead3c4b32af30,
title = "Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients",
abstract = "Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95{\%} Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB.",
author = "Leone, {Maurizio A.} and Nadia Barizzone and Federica Esposito and Ausiliatrice Lucenti and Harbo, {Hanne F.} and An Goris and Ingrid Kockum and Oturai, {Annette Bang} and Celius, {Elisabeth Gulowsen} and Mero, {Inger L.} and B{\'e}n{\'e}dicte Dubois and Tomas Olsson and S{\o}ndergaard, {Helle Bach} and Daniele Cusi and Sara Lupoli and Andreassen, {Bettina Kulle} and L. Barcellos and D. Booth and M. Comabella and A. Compston and S. D'Alfonso and {De Jager}, P. and B. Fontaine and A. Goris and D. Hafler and J. Haines and Harbo, {H. F.} and Hauser, {S. L.} and C. Hawkins and B. Hemmer and J. Hillert and A. Ivinson and McCauley, {Jacob L} and R. Martin and {Martinelli Boneschi}, F. and McCauley, {J. L.} and Pericak-Vance, {Margaret A} and T. Olsson and A. Oturai and N. Patsopoulos and M. Pericak-Vance and J. Saarela and S. Sawcer and A. Spurkland and G. Stewart and F. Zipp and Myhr, {Kjell Morten} and Guerini, {Franca R.} and Paola Naldi and Daniela Galimberti and Elio Scarpini and Roberto Bergamaschi and {Di Sapio}, Antonella and Domenico Caputo and Gabriella Rosso and Susanna Cordera and Paola Cavalla and Roberto Cavallo and Benedetti, {Maria D.} and Marco Salvetti and Ruggero Capra and Angelo Ghezzi and Pietro Annovazzi and Gabriella Coniglio and Giuseppe Liberatore and Mariaemma Rodegher and Lucia Moiola and Bruno Colombo and Marta Radaelli and Paolo Rossi and Vittorio Martinelli and Giancarlo Comi and Filippo Martinelli-Boneschi and Sandra D'Alfonso",
year = "2013",
month = "6",
day = "13",
doi = "10.1371/journal.pone.0064408",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

AU - Leone, Maurizio A.

AU - Barizzone, Nadia

AU - Esposito, Federica

AU - Lucenti, Ausiliatrice

AU - Harbo, Hanne F.

AU - Goris, An

AU - Kockum, Ingrid

AU - Oturai, Annette Bang

AU - Celius, Elisabeth Gulowsen

AU - Mero, Inger L.

AU - Dubois, Bénédicte

AU - Olsson, Tomas

AU - Søndergaard, Helle Bach

AU - Cusi, Daniele

AU - Lupoli, Sara

AU - Andreassen, Bettina Kulle

AU - Barcellos, L.

AU - Booth, D.

AU - Comabella, M.

AU - Compston, A.

AU - D'Alfonso, S.

AU - De Jager, P.

AU - Fontaine, B.

AU - Goris, A.

AU - Hafler, D.

AU - Haines, J.

AU - Harbo, H. F.

AU - Hauser, S. L.

AU - Hawkins, C.

AU - Hemmer, B.

AU - Hillert, J.

AU - Ivinson, A.

AU - McCauley, Jacob L

AU - Martin, R.

AU - Martinelli Boneschi, F.

AU - McCauley, J. L.

AU - Pericak-Vance, Margaret A

AU - Olsson, T.

AU - Oturai, A.

AU - Patsopoulos, N.

AU - Pericak-Vance, M.

AU - Saarela, J.

AU - Sawcer, S.

AU - Spurkland, A.

AU - Stewart, G.

AU - Zipp, F.

AU - Myhr, Kjell Morten

AU - Guerini, Franca R.

AU - Naldi, Paola

AU - Galimberti, Daniela

AU - Scarpini, Elio

AU - Bergamaschi, Roberto

AU - Di Sapio, Antonella

AU - Caputo, Domenico

AU - Rosso, Gabriella

AU - Cordera, Susanna

AU - Cavalla, Paola

AU - Cavallo, Roberto

AU - Benedetti, Maria D.

AU - Salvetti, Marco

AU - Capra, Ruggero

AU - Ghezzi, Angelo

AU - Annovazzi, Pietro

AU - Coniglio, Gabriella

AU - Liberatore, Giuseppe

AU - Rodegher, Mariaemma

AU - Moiola, Lucia

AU - Colombo, Bruno

AU - Radaelli, Marta

AU - Rossi, Paolo

AU - Martinelli, Vittorio

AU - Comi, Giancarlo

AU - Martinelli-Boneschi, Filippo

AU - D'Alfonso, Sandra

PY - 2013/6/13

Y1 - 2013/6/13

N2 - Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB.

AB - Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB.

UR - http://www.scopus.com/inward/record.url?scp=84879052306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879052306&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0064408

DO - 10.1371/journal.pone.0064408

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e64408

ER -