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Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

Genes & Immunity volume 12, pages 110–115 (2011)Cite this article

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Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P=1.6 × 10−5; odds ratio (95% confidence interval)=1.23 (1.12–1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care.

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Acknowledgements

We thank patients with multiple sclerosis and control subjects for making this study feasible. Financial support for the study was provided by: Ministerio de Ciencia e Innovación-Feder (SAF2009-11491), Fondo de Investigación Sanitaria FIS (RETICS-REEM RD07/0060, PI0902105, PI081636, PI070353) Junta de Andalucía (P07-CVI-02551), Fundación Ilundain, and Ikerbasque, the Basque Foundation for Science (Bilbao). SNP genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado’ CEGEN-USC, www.cegen.org.

Author information

Author notes

  1. M L Cavanillas, O Fernández, M Comabella, F Matesanz and E Urcelay: These authors contributed equally to this work.

Authors and Affiliations

  1. Immunology Department Hospital Clínico S. Carlos, Madrid, Spain

    M L Cavanillas, M C Cénit & E Urcelay

  2. Inst. de Neurociencias Clínicas, Hospital Carlos Haya, Málaga, Spain

    O Fernández & C L Gómez

  3. Centre d’Esclerosi Múltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d’Hebron (HUVH), Barcelona, Spain

    M Comabella & X Montalbán

  4. Instituto de Parasitología y Biomedicina ‘López Neyra’, C. S. I. C., Granada, Spain

    A Alcina, M Fedetz & F Matesanz

  5. Unidad de Esclerosis Múltiple. Hospital Virgen Macarena, Sevilla, Spain

    G Izquierdo

  6. Servicio de Biología Molecular. Hospital Virgen Macarena, Sevilla, Spain

    M Lucas

  7. Neurology Department, Multiple Sclerosis Unit, Hospital Clínico S. Carlos, Madrid, Spain

    R Arroyo

  8. Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain

    K Vandenbroeck & I Alloza

  9. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

    K Vandenbroeck

  10. Servicio de Genética, Hospital de Basurto, Bilbao, Spain

    M García-Barcina

  11. Servicio de Neurología, Hospital de Basurto, Bilbao, Spain

    A Antigüedad

  12. Laboratorio de Investigación, Hospital Civil, Málaga, Spain

    L Leyva

  13. Servicio de Neurología, Unidad de Esclerosis Múltiple, Hospital Donostia, San Sebastián, Spain

    J Olascoaga

  14. Área de Neurociencias, Insti. Investigación Sanitaria Biodonostia, San Sebastián, Spain

    D Otaegui

  15. Neurology Service, Hospital Clinic and Institut d’Investigació Biomèdica Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Y Blanco & A Saiz

Authors
  1. M L Cavanillas
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  2. O Fernández
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  3. M Comabella
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  4. A Alcina
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  5. M Fedetz
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  6. G Izquierdo
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  7. M Lucas
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  8. M C Cénit
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  9. R Arroyo
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  10. K Vandenbroeck
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  11. I Alloza
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  12. M García-Barcina
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  13. A Antigüedad
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  14. L Leyva
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  15. C L Gómez
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  16. J Olascoaga
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  17. D Otaegui
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  18. Y Blanco
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  19. A Saiz
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  20. X Montalbán
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  21. F Matesanz
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  22. E Urcelay
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Corresponding author

Correspondence to E Urcelay.

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Cavanillas, M., Fernández, O., Comabella, M. et al. Replication of top markers of a genome-wide association study in multiple sclerosis in Spain. Genes Immun 12, 110–115 (2011). https://doi.org/10.1038/gene.2010.52

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  • DOI: https://doi.org/10.1038/gene.2010.52

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