Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward,
establishing the biology underlying these associations has proven extremely difficult. Even
determining which cell types and which particular gene(s) are relevant continues to be a
challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple
sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls
and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan
immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes.
Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the
individual genetic risk to MS. This approach could be adopted in any other complex trait for
which genome-wide data is available