@article {Lill848, author = {Christina M Lill and Felix Luessi and Antonio Alcina and Ekaterina A Sokolova and Nerea Ugidos and Bel{\'e}n de la Hera and L{\'e}na Guillot-No{\"e}l and Sunny Malhotra and Eva Reinthaler and Brit-Maren M Schjeide and Julia Y Mescheriakova and Andriy Mashychev and Inken Wohlers and Denis A Akkad and Orhan Aktas and Iraide Alloza and Alfredo Antig{\"u}edad and Rafa Arroyo and Ianire Astobiza and Paul Blaschke and Alexei N Boyko and Mathias Buttmann and Andrew Chan and Thomas D{\"o}rner and Joerg T Epplen and Olga O Favorova and Maria Fedetz and Oscar Fern{\'a}ndez and Angel Garc{\'\i}a-Mart{\'\i}nez and Lisa-Ann Gerdes and Christiane Graetz and Hans-Peter Hartung and Sabine Hoffjan and Guillermo Izquierdo and Denis S Korobko and Antje Kroner and Christian Kubisch and Tania K{\"u}mpfel and Laura Leyva and Peter Lohse and Nadezhda A Malkova and Xavier Montalban and Ekaterina V Popova and Peter Rieckmann and Alexei S Rozhdestvenskii and Christiane Schmied and Inna V Smagina and Ekaterina Y Tsareva and Alexander Winkelmann and Uwe K Zettl and Harald Binder and Isabelle Cournu-Rebeix and Rogier Hintzen and Alexander Zimprich and Manuel Comabella and Bertrand Fontaine and Elena Urcelay and Koen Vandenbroeck and Maxim Filipenko and Fuencisla Matesanz and Frauke Zipp and Lars Bertram}, title = {Genome-wide significant association with seven novel multiple sclerosis risk loci}, volume = {52}, number = {12}, pages = {848--855}, year = {2015}, doi = {10.1136/jmedgenet-2015-103442}, publisher = {BMJ Publishing Group Ltd}, abstract = {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{\texttimes}10-8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03{\texttimes}10-12), CD28 (rs6435203, p=1.35{\texttimes}10-9), LPP (rs4686953, p=3.35{\texttimes}10-8), ETS1 (rs3809006, p=7.74{\texttimes}10-9), DLEU1 (rs806349, p=8.14{\texttimes}10-12), LPIN3 (rs6072343, p=7.16{\texttimes}10-12) and IFNGR2 (rs9808753, p=4.40{\texttimes}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.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/52/12/848}, eprint = {https://jmg.bmj.com/content/52/12/848.full.pdf}, journal = {Journal of Medical Genetics} }