title: Validation of the CD6 and TNFRSF1A loci as risk factors for multiple sclerosis in Spain.
abstract: A recent meta-analysis of genome-wide association screens coupled to a replication exercise in a combined US/UK collection led to the identification of 4 single nucleotide polymorphisms (SNPs) in three gene loci, i.e. TNFRSF1A, CD6 and IRF8, as novel risk factors for multiple sclerosis with genome-wide level of significance. In the present study, using a combined all-Spain collection of 2515 MS patients and 2942 healthy controls, we demonstrate significant association of rs17824933 in CD6 (P(CMH)=0.004; OR=1.14; 95% CI 1.04-1.24) and of rs1860545 in TNFRSF1A (P(CMH)=0.001; OR=1.15; 95% CI 1.06-1.25) with MS, while the low-frequency coding non-synonymous SNP rs4149584 in TNFRSF1A displayed a trend for association (P(CMH)=0.062; OR=1.27; 95% CI 0.99-1.63). This data reinforce a generic role for CD6 and TNFRSF1A in susceptibility to MS, extending to populations of southern European ancestry.
authors.affiliation: Neurogenomiks Laboratory, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Bhairavi
authors.initials: B
authors.lastname: Swaminathan
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
authors.forename: Mariá L
authors.initials: ML
authors.lastname: Cavanillas
authors.forename: Iraide
authors.initials: I
authors.lastname: Alloza
authors.forename: David
authors.initials: D
authors.lastname: Otaegui
authors.forename: Javier
authors.initials: J
authors.lastname: Olascoaga
authors.forename: María C
authors.initials: MC
authors.lastname: Cénit
authors.forename: Virgina
authors.initials: V
authors.lastname: de las Heras
authors.forename: María García
authors.initials: MG
authors.lastname: Barcina
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernandez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Antigüedad
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D056426:Genetic Loci / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human