A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

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http://hdl.handle.net/10138/303713

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Intl Multiple Sclerosis Genetics , Madireddy , L , Patsopoulos , N A & Palotie , A 2019 , ' A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis ' , Nature Communications , vol. 10 , 2236 . https://doi.org/10.1038/s41467-019-09773-y

Title: A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
Author: Intl Multiple Sclerosis Genetics; Madireddy, Lohith; Patsopoulos, Niklaos A.; Palotie, Aarno
Contributor: University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2019-05-20
Language: eng
Number of pages: 12
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/303713
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 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.
Subject: GENOME-WIDE ASSOCIATION
POLYGENIC RISK SCORE
GWAS
EXPRESSION
CYTOSCAPE
PATHWAY
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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