Genome wide association study in 9772 multiple sclerosis cases from 15 countries, European ( 7597), USA (1382), Australia (647) and New Zealand (146), compared to 11479 European and 5370 USA controls. Cases and controls were of self-reported European ancestry. Case characteristic/diagnostic: Age at onset between 26.8 - 37.8 with a mean of 32.3, Expanded Disability Status Score (EDSS) mean 3.9, Multiple Sclerosis Severity Score (MSSS) mean 4.9. Genotyping was performed on the Illumina platform and 465434 SNPs were available for analysis. Replication was done “in silico” using data from previously published GWAS, performed on a mixture of genotyping platforms. Replication analysis included data from 4218 cases and 7296 controls. Genotypes at untyped markers were imputed using data from HapMap phase II (release 22) and the software package MACH. 102 SNPs from the new Genome wide association study were tested in the replication data set and 29 novel loci were confirmed in addition to confirming the 23 of the 26 previously known loci. GWAS p-value threshold (for 29 novel regions): Combined p-value < 5.0E-08.
- Minor allele frequency > 0.1%
- Call rate > 98% (for external control data)
- Plate association p-value > 1E-50 (for shared control data and internal MS data)
- Hardy-Weinberg p-value > 1E-50 (for shared control data & internal MS data) and p-value > 1E-20 (for external control data)
- Additional filters: Automated cluster checks and Beta-binomial modelling approaches were applied.
GDXHsS00007 meets the following criteria: