A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
Comabella López, Manuel (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Gene Expression Regulation ; Genes, Regulator ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Multiple Sclerosis ; Polymorphism, Single Nucleotide ; Systems Biology
Publicat a:	Nature communications, Vol. 10 Núm. 1 (20 2019) , p. 2236, ISSN 2041-1723

DOI: 10.1038/s41467-019-09773-y
PMID: 31110181

12 p, 2.9 MB

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