RT Journal Article
SR Electronic
T1 The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 143933
DO 10.1101/143933
A1 International Multiple Sclerosis Genetics Consortium
A1 NA Patsopoulos
A1 SE Baranzini
A1 A Santaniello
A1 P Shoostari
A1 C Cotsapas
A1 G Wong
A1 AH Beecham
A1 T James
A1 J Replogle
A1 I Vlachos
A1 C McCabe
A1 T Pers
A1 A Brandes
A1 C White
A1 B Keenan
A1 M Cimpean
A1 P Winn
A1 IP Panteliadis
A1 A Robbins
A1 TFM Andlauer
A1 O Zarzycki
A1 B Dubois
A1 A Goris
A1 H Bach Sondergaard
A1 F Sellebjerg
A1 P Soelberg Sorensen
A1 H Ullum
A1 L Wegner Thoerner
A1 J Saarela
A1 I Cournu Rebeix
A1 V Damotte
A1 B Fontaine
A1 L Guillot Noel
A1 M Lathrop
A1 S Vukusik
A1 A Berthele
A1 V Biberacher
A1 D Buck
A1 C Gasperi
A1 C Graetz
A1 V Grummel
A1 B Hemmer
A1 M Hoshi
A1 B Knier
A1 T Korn
A1 CM Lill
A1 F Luessi
A1 M Mühlau
A1 F Zipp
A1 E Dardiotis
A1 C Agliardi
A1 A Amoroso
A1 N Barizzone
A1 MD Benedetti
A1 L Bernardinelli
A1 P Cavalla
A1 F Clarelli
A1 G Comi
A1 D Cusi
A1 F Esposito
A1 L Ferrè
A1 D Galimberti
A1 C Guaschino
A1 MA Leone
A1 V Martinelli
A1 L Moiola
A1 M Salvetti
A1 M Sorosina
A1 D Vecchio
A1 A Zauli
A1 S Santoro
A1 M Zuccalà
A1 J Mescheriakova
A1 C van Duijn
A1 SD Bos
A1 EG Celius
A1 A Spurkland
A1 M Comabella
A1 X Montalban
A1 L Alfredsson
A1 I Bomfim
A1 D Gomez-Cabrero
A1 J Hillert
A1 M Jagodic
A1 M Lindén
A1 F Piehl
A1 I Jelčić
A1 R Martin
A1 M Sospedra
A1 A Baker
A1 M Ban
A1 C Hawkins
A1 P Hysi
A1 S Kalra
A1 F Karpe
A1 J Khadake
A1 G Lachance
A1 P Molyneux
A1 M Neville
A1 J Thorpe
A1 E Bradshaw
A1 SJ Caillier
A1 P Calabresi
A1 BAC Cree
A1 A Cross
A1 M Davis
A1 PWI de Bakker
A1 S Delgado
A1 M Dembele
A1 K Edwards
A1 K Fitzgerald
A1 IY Frohlich
A1 PA Gourraud
A1 JL Haines
A1 H Hakonarson
A1 D Kimbrough
A1 N Isobe
A1 I Konidari
A1 E Lathi
A1 MH Lee
A1 T Li
A1 D An
A1 A Zimmer
A1 A Lo
A1 L Madireddy
A1 CP Manrique
A1 M Mitrovic
A1 M Olah
A1 E Patrick
A1 MA Pericak-Vance
A1 L Piccio
A1 C Schaefer
A1 H Weiner
A1 K Lage
A1 A Compston
A1 D Hafler
A1 HF Harbo
A1 SL Hauser
A1 G Stewart
A1 S D’Alfonso
A1 G Hadjigeorgiou
A1 B Taylor
A1 LF Barcellos
A1 D Booth
A1 R Hintzen
A1 I Kockum
A1 F Martinelli-Boneschi
A1 JL McCauley
A1 JR Oksenberg
A1 A Oturai
A1 S Sawcer
A1 AJ Ivinson
A1 T Olsson
A1 PL De Jager
A1 Murray Barclay
A1 Laurent Peyrin-Biroulet
A1 Mathias Chamaillard
A1 Jean-Frederick Colombe
A1 Mario Cottone
A1 Anthony Croft
A1 Renata D’Incà
A1 Jonas Halfvarson
A1 Katherine Hanigan
A1 Paul Henderson
A1 Jean-Pierre Hugot
A1 Amir Karban
A1 Nicholas A Kennedy
A1 Mohammed Azam Khan
A1 Marc Lémann
A1 Arie Levine
A1 Dunecan Massey
A1 Monica Milla
A1 Grant W Montgomery
A1 Sok Meng Evelyn Ng
A1 Ioannis Oikonomou
A1 Harald Peeters
A1 Deborah D. Proctor
A1 Jean-Francois Rahier
A1 Rebecca Roberts
A1 Paul Rutgeerts
A1 Frank Seibold
A1 Laura Stronati
A1 Kirstin M Taylor
A1 Leif Törkvist
A1 Kullak Ublick
A1 Johan Van Limbergen
A1 Andre Van Gossum
A1 Morten H. Vatn
A1 Hu Zhang
A1 Wei Zhang
A1 Australia and New Zealand IBDGC
A1 Belgium Genetic Consortium
A1 Initiative on Crohn and Colitis
A1 NIDDK IBDGC
A1 United Kingdom IBDGC
A1 Wellcome Trust Case Control Consortium
YR 2017
UL http://biorxiv.org/content/early/2017/07/13/143933.abstract
AB We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.One Sentence Summary: We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.