Genome-wide significant association with seven novel multiple sclerosis risk loci
| Autor: | Alexei S Rozhdestvenskii, Bertrand Fontaine, Lisa-Ann Gerdes, Rogier Q. Hintzen, Brit-Maren M. Schjeide, Maxim L. Filipenko, Isabelle Cournu-Rebeix, Xavier Montalban, Joerg T. Epplen, Manuel Comabella, Antonio Alcina, Ekaterina Popova, Elena Urcelay, Denis A. Akkad, Sabine Hoffjan, Christina M. Lill, Uwe K. Zettl, Koen Vandenbroeck, Oscar Fernández, Nerea Ugidos, Peter Lohse, Harald Binder, Felix Luessi, I. V. Smagina, Mathias Buttmann, D. S. Korobko, Alexander Winkelmann, Sunny Malhotra, Lena Guillot-Noel, Christian Kubisch, Frauke Zipp, Thomas Dörner, Ekaterina Yu. Tsareva, Christiane Graetz, María Fedetz, O O Favorova, Christiane Schmied, Iraide Alloza, Inken Wohlers, Angel Garcia-Martinez, Belén de la Hera, Ekaterina A. Sokolova, Alexander Zimprich, Peter Rieckmann, Ianire Astobiza, Andriy Mashychev, Alfredo Antigüedad, Guillermo Izquierdo, Julia Y Mescheriakova, R. Arroyo, Paul Blaschke, Hans-Peter Hartung, Fuencisla Matesanz, Lars Bertram, Antje Kroner, Orhan Aktas, Tania Kümpfel, Laura Leyva, A N Boyko, N A Malkova, Eva M. Reinthaler, Andrew T. Chan |
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| Přispěvatelé: | Neurology |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Genetics
Multiple Sclerosis Multiple sclerosis Case-control study Single-nucleotide polymorphism Locus (genetics) Genome-wide association study Biology medicine.disease Logistic regression Polymorphism Single Nucleotide Gene Frequency Genetic Loci Risk Factors Case-Control Studies medicine Humans Genetic Predisposition to Disease Allele frequency Genetics (clinical) Genome-Wide Association Study Genetic association |
| Zdroj: | Journal of Medical Genetics, 52(12), 848-855. BMJ Publishing Group |
| ISSN: | 0022-2593 |
| Popis: | 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 −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. |
| Databáze: | OpenAIRE |
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