TY - JOUR T1 - Genome-wide significant association with seven novel multiple sclerosis risk loci JF - Journal of Medical Genetics JO - J Med Genet SP - 848 LP - 855 DO - 10.1136/jmedgenet-2015-103442 VL - 52 IS - 12 AU - Christina M Lill AU - Felix Luessi AU - Antonio Alcina AU - Ekaterina A Sokolova AU - Nerea Ugidos AU - Belén de la Hera AU - Léna Guillot-Noël AU - Sunny Malhotra AU - Eva Reinthaler AU - Brit-Maren M Schjeide AU - Julia Y Mescheriakova AU - Andriy Mashychev AU - Inken Wohlers AU - Denis A Akkad AU - Orhan Aktas AU - Iraide Alloza AU - Alfredo Antigüedad AU - Rafa Arroyo AU - Ianire Astobiza AU - Paul Blaschke AU - Alexei N Boyko AU - Mathias Buttmann AU - Andrew Chan AU - Thomas Dörner AU - Joerg T Epplen AU - Olga O Favorova AU - Maria Fedetz AU - Oscar Fernández AU - Angel García-Martínez AU - Lisa-Ann Gerdes AU - Christiane Graetz AU - Hans-Peter Hartung AU - Sabine Hoffjan AU - Guillermo Izquierdo AU - Denis S Korobko AU - Antje Kroner AU - Christian Kubisch AU - Tania Kümpfel AU - Laura Leyva AU - Peter Lohse AU - Nadezhda A Malkova AU - Xavier Montalban AU - Ekaterina V Popova AU - Peter Rieckmann AU - Alexei S Rozhdestvenskii AU - Christiane Schmied AU - Inna V Smagina AU - Ekaterina Y Tsareva AU - Alexander Winkelmann AU - Uwe K Zettl AU - Harald Binder AU - Isabelle Cournu-Rebeix AU - Rogier Hintzen AU - Alexander Zimprich AU - Manuel Comabella AU - Bertrand Fontaine AU - Elena Urcelay AU - Koen Vandenbroeck AU - Maxim Filipenko AU - Fuencisla Matesanz AU - Frauke Zipp AU - Lars Bertram Y1 - 2015/12/01 UR - http://jmg.bmj.com/content/52/12/848.abstract N2 - Objective A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors.Methods The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis.Results Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus.Conclusions This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases. ER -