A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
- Madireddy, L
- Patsopoulos, NA
- Cotsapas, C
- Bos, SD
- Beecham, A
- McCauley, J
- Kim, K
- Jia, XM
- Santaniello, A
- Caillier, SJ
- Andlauer, TFM
- Barcellos, LF
- Berge, T
- Bernardinelli, L
- Martinelli-Boneschi, F
- Booth, DR
- Briggs, F
- Celius, EG
- Comabella, M
- Comi, G
- Cree, BAC
- D'Alfonso, S
- Dedham, K
- Duquette, P
- Efthimios, D
- Esposito, F
- Fontaine, B
- Gasperi, C
- Goris, A
- Dubois, B
- Gourraud, PA
- Hadjigeorgiou, G
- Haines, J
- Hawkins, C
- Hemmer, B
- Hintzen, R
- Horakova, D
- Isobe, N
- Kalra, S
- Kira, J
- Khalil, M
- Kockum, I
- Lill, CM
- Lincoln, MR
- Luessi, F
- Martin, R
- Oturai, A
- Palotie, A
- Pericak-Vance, MA
- Henry, R
- Saarela, J
- Ivinson, A
- Olsson, T
- Taylor, BV
- Stewart, GJ
- Harbo, HF
- Compston, A
- Hauser, SL
- Hafler, DA
- Zipp, F
- De Jager, P
- Sawcer, S
- Oksenberg, JR
- Baranzini, SE
DOIAbstract
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 pat...
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