Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
Authors:   International Multiple Sclerosis Genetics Consortium, Patsopoulos Nikolaos A. , Baranzini Sergio E. , Santaniello Adam , Shoostari Parisa , Cotsapas Chris , Wong Garrett , Beecham Ashley H. , James Tojo , Replogle Joseph , Vlachos Ioannis S. , McCabe Cristin , Pers Tune H. , Brandes Aaron , White Charles , Keenan Brendan , Cimpean Maria , Winn Phoebe , Panteliadis Ioannis-Pavlos , Robbins Allison , Andlauer Till F. M. , Zarzycki Onigiusz , Dubois Bénédicte , Goris An , Søndergaard Helle Bach , Sellebjerg Finn , Sorensen Per Soelberg , Ullum Henrik , Thørner Lise Wegner , Saarela Janna , Cournu-Rebeix Isabelle , Damotte Vincent , Fontaine Bertrand , Guillot-Noel Lena , Lathrop Mark , Vukusic Sandra , Berthele Achim , Pongratz Viola , Buck Dorothea , Gasperi Christiane , Graetz Christiane , Grummel Verena , Hemmer Bernhard , Hoshi Muni , Knier Benjamin , Korn Thomas , Lill Christina M. , Luessi Felix , Mühlau Mark , Zipp Frauke , Dardiotis Efthimios , Agliardi Cristina , Amoroso Antonio , Barizzone Nadia , Benedetti Maria D. , Bernardinelli Luisa , Cavalla Paola , Clarelli Ferdinando , Comi Giancarlo , Cusi Daniele , Esposito Federica , Ferrè Laura , Galimberti Daniela , Guaschino Clara , Leone Maurizio A. , Martinelli Vittorio , Moiola Lucia , Salvetti Marco , Sorosina Melissa , Vecchio Domizia , Zauli Andrea , Santoro Silvia , Mancini Nicasio , Zuccalà Miriam , Mescheriakova Julia , van Duijn Cornelia , Bos Steffan D. , Celius Elisabeth G. , Spurkland Anne , Comabella Manuel , Montalban Xavier , Alfredsson Lars , Bomfim Izaura L. , Gomez-Cabrero David , Hillert Jan , Jagodic Maja , Lindén Magdalena , Piehl Fredrik , Jelčić Ilijas , Martin Roland , Sospedra Mirela , Baker Amie , Ban Maria , Hawkins Clive , Hysi Pirro , Kalra Seema , Karpe Fredrik , Khadake Jyoti , Lachance Genevieve , Molyneux Paul , Neville Matthew , Thorpe John , Bradshaw Elizabeth , Caillier Stacy J. , Calabresi Peter , Cree Bruce A. C. , Cross Anne , Davis Mary , de Bakker Paul W. I. , Delgado Silvia , Dembele Marieme , Edwards Keith , Fitzgerald Kate , Frohlich Irene Y. , Gourraud Pierre-Antoine , Haines Jonathan L , Hakonarson Hakon , Kimbrough Dorlan , Isobe Noriko , Konidari Ioanna , Lathi Ellen , Lee Michelle H. , Li Taibo , An David , Zimmer Andrew , Madireddy Lohith , Manrique Clara P. , Mitrovic Mitja , Olah Marta , Patrick Ellis , Pericak-Vance Margaret A. , Piccio Laura , Schaefer Cathy , Weiner Howard , Lage Kasper ,   ANZgene,   IIBDGC,   WTCCC2, Compston Alastair , Hafler David , Harbo Hanne F. , Hauser Stephen L. , Stewart Graeme , D’Alfonso Sandra , Hadjigeorgiou Georgios , Taylor Bruce , Barcellos Lisa F. , Booth David , Hintzen Rogier , Kockum Ingrid , Martinelli-Boneschi Filippo , McCauley Jacob L. , Oksenberg Jorge R. , Oturai Annette , Sawcer Stephen , Ivinson Adrian J. , Olsson Tomas , De Jager Philip L. 
Published: September 2019

Genetic roots of multiple sclerosis

The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis.

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