TY - JOUR
T1 - A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
AU - International Multiple Sclerosis Genetics Consortium
AU - Madireddy, Lohith
AU - Patsopoulos, Niklaos A.
AU - Cotsapas, Chris
AU - Bos, Steffan D.
AU - Beecham, Ashley
AU - McCauley, Jacob
AU - Kim, Kicheol
AU - Jia, Xiaoming
AU - Santaniello, Adam
AU - Caillier, Stacy J.
AU - Andlauer, Till F.M.
AU - Barcellos, Lisa F.
AU - Berge, Tone
AU - Bernardinelli, Luisa
AU - Martinelli-Boneschi, Filippo
AU - Booth, David R.
AU - Briggs, Farren
AU - Celius, Elisabeth G.
AU - Comabella, Manuel
AU - Comi, Giancarlo
AU - Cree, Bruce A.C.
AU - D’Alfonso, Sandra
AU - Dedham, Katrina
AU - Duquette, Pierre
AU - Efthimios, Dardiotis
AU - Esposito, Federica
AU - Fontaine, Bertrand
AU - Gasperi, Christiane
AU - Goris, An
AU - Dubois, Bénédicte
AU - Gourraud, Pierre Antoine
AU - Hadjigeorgiou, Georgios
AU - Haines, Jonathan
AU - Hawkins, Clive
AU - Hemmer, Bernhard
AU - Hintzen, Rogier
AU - Horakova, Dana
AU - Isobe, Noriko
AU - Kalra, Seema
AU - Kira, Jun ichi
AU - Khalil, Michael
AU - Kockum, Ingrid
AU - Lill, Christina M.
AU - Lincoln, Matthew R R.
AU - Luessi, Felix
AU - Martin, Roland
AU - Oturai, Annette
AU - Palotie, Aarno
AU - Pericak-Vance, Margaret A.
AU - Henry, Roland
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85066046672&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-09773-y
DO - 10.1038/s41467-019-09773-y
M3 - Article
C2 - 31110181
AN - SCOPUS:85066046672
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2236
ER -