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

M. L. Cavanillas; O. Fernández; M. Comabella; A. Alcina; M. Fedetz; G. Izquierdo; M. Lucas; M. C. Cénit; R. Arroyo; K. Vandenbroeck; I. Alloza; M. García-Barcina; A. Antigüedad; L. Leyva; C. L. Gómez; J. Olascoaga; D. Otaegui; Y. Blanco; A. Saiz; X. Montalbán; F. Matesanz; E. Urcelay

doi:10.1038/gene.2010.52

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

M. L. Cavanillas, O. Fernández, M. Comabella, A. Alcina, M. Fedetz, G. Izquierdo, M. Lucas, M. C. Cénit, R. Arroyo, K. Vandenbroeck, I. Alloza, M. García-Barcina, A. Antigüedad, L. Leyva, C. L. Gómez, J. Olascoaga, D. Otaegui, Y. Blanco, A. Saiz, X. MontalbánF. Matesanz, E. Urcelay^*

^*Autor corresponent d’aquest treball

Departament de Medicina

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

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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.

Idioma original	Anglès
Pàgines (de-a)	110-115
Nombre de pàgines	6
Revista	Genes and Immunity
Volum	12
Número	2
DOIs	https://doi.org/10.1038/gene.2010.52
Estat de la publicació	Publicada - de març 2011

SDG de les Nacions Unides

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10.1038/gene.2010.52

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Cavanillas, M. L., Fernández, O., Comabella, M., Alcina, A., Fedetz, M., Izquierdo, G., Lucas, M., Cénit, M. C., Arroyo, R., Vandenbroeck, K., Alloza, I., García-Barcina, M., Antigüedad, A., Leyva, L., Gómez, C. L., Olascoaga, J., Otaegui, D., Blanco, Y., Saiz, A., ... Urcelay, E. (2011). Replication of top markers of a genome-wide association study in multiple sclerosis in Spain. Genes and Immunity, 12(2), 110-115. https://doi.org/10.1038/gene.2010.52

@article{c5569ab9de7b48408d30ad6ba11e8f09,

title = "Replication of top markers of a genome-wide association study in multiple sclerosis in Spain",

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.",

keywords = "genetics, GPC5, GWAS, multiple sclerosis",

author = "Cavanillas, {M. L.} and O. Fern{\'a}ndez and M. Comabella and A. Alcina and M. Fedetz and G. Izquierdo and M. Lucas and C{\'e}nit, {M. C.} and R. Arroyo and K. Vandenbroeck and I. Alloza and M. Garc{\'i}a-Barcina and A. Antig{\"u}edad and L. Leyva and G{\'o}mez, {C. L.} and J. Olascoaga and D. Otaegui and Y. Blanco and A. Saiz and X. Montalb{\'a}n and F. Matesanz and E. Urcelay",

note = "Funding Information: 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 Innovaci{\'o}n-Feder (SAF2009-11491), Fondo de Investiga-ci{\'o}n Sanitaria FIS (RETICS-REEM RD07/0060, PI0902105, PI081636, PI070353) Junta de Andaluc{\'i}a (P07-CVI-02551), Fundaci{\'o}n Ilundain, and Ikerbasque, the Basque Foundation for Science (Bilbao). SNP genotyping services were provided by the Spanish {\textquoteleft}Centro Nacional de Genotipado{\textquoteright} CEGEN-USC, www.cegen.org.",

year = "2011",

month = mar,

doi = "10.1038/gene.2010.52",

language = "English",

volume = "12",

pages = "110--115",

journal = "Genes and Immunity",

issn = "1466-4879",

number = "2",

}

Cavanillas, ML, Fernández, O, Comabella, M, Alcina, A, Fedetz, M, Izquierdo, G, Lucas, M, Cénit, MC, Arroyo, R, Vandenbroeck, K, Alloza, I, García-Barcina, M, Antigüedad, A, Leyva, L, Gómez, CL, Olascoaga, J, Otaegui, D, Blanco, Y, Saiz, A, Montalbán, X, Matesanz, F & Urcelay, E 2011, 'Replication of top markers of a genome-wide association study in multiple sclerosis in Spain', Genes and Immunity, vol. 12, núm. 2, pàg. 110-115. https://doi.org/10.1038/gene.2010.52

TY - JOUR

T1 - Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

AU - Cavanillas, M. L.

AU - Fernández, O.

AU - Comabella, M.

AU - Alcina, A.

AU - Fedetz, M.

AU - Izquierdo, G.

AU - Lucas, M.

AU - Cénit, M. C.

AU - Arroyo, R.

AU - Vandenbroeck, K.

AU - Alloza, I.

AU - García-Barcina, M.

AU - Antigüedad, A.

AU - Leyva, L.

AU - Gómez, C. L.

AU - Olascoaga, J.

AU - Otaegui, D.

AU - Blanco, Y.

AU - Saiz, A.

AU - Montalbán, X.

AU - Matesanz, F.

AU - Urcelay, E.

N1 - Funding Information: 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 Investiga-ción 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.

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - genetics

KW - GPC5

KW - GWAS

KW - multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=79952282726&partnerID=8YFLogxK

U2 - 10.1038/gene.2010.52

DO - 10.1038/gene.2010.52

M3 - Article

AN - SCOPUS:79952282726

SN - 1466-4879

VL - 12

SP - 110

EP - 115

JO - Genes and Immunity

JF - Genes and Immunity

IS - 2

ER -

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

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