Genetics of MSThursday, October 03, 2013, 11:25 - 11:37
Towards completing the map of common genetic variation in multiple sclerosisN.A. Patsopoulos on behalf of the International Multiple Sclerosis Genetics Consortium
We present results of the International Multiple Sclerosis Genetics Consortiumís (IMSGC) analysis of ~8 million SNPs in each of 14,802 multiple sclerosis (MS) cases and 26,703 controls. This deep genome-wide discovery phase yielded 88 statistical independent effects at the genome-wide level (p-value < 5 x 10-08), and another 126 suggestive effects at p-value < 10-5. Further, in 36 of these loci, we find evidence of multiple variants that have statistically independent effects with MS susceptibility. This large sample size allows us to quantify the exact variance explained by each susceptibility allele using multivariate models and to estimate the overall contribution of common genetic variability to MS susceptibility. Finally, we describe the design of the replication phase in 18,000 cases and 18,000 controls and the preliminary joint summary results.
In an effort to organize the identified effects, we integrate the results with data relating the effect of each SNP on RNA expression of nearby genes in three different sets of immune cells, and genome-wide epigenomic data from the ENCODE project that characterizes the state of chromatin in over 300 different cell types enables us to nominate the most likely candidate causal variant in each locus. Further, these data suggest that while many MS susceptibility alleles affect primarily adaptive immune function, an equivalent number of alleles affect innate immune function. Thus, we find that both arms of the immune system are strongly implicated in MS susceptibility.
By performing the largest experiment to date in the genetic analysis of common variation in MS, we describe and functionally annotate the most complete genetic map of MS susceptibility.
nothing to disclose