Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

International Multiple Sclerosis Genetics Consortium.
A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.
Nat Commun. 2019; 10(1): 2236-2236. Doi: 10.1038/s41467-019-09773-y [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Co-Autor*innen der Med Uni Graz

Khalil Michael

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Abstract:

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 intra-individual 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.

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