NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk

Jack Antel, Maria Ban, Sergio Baranzini, Lisa Barcellos, Nadia Barizzone, Ashley Beecham, Tone Berge, Luisa Bernardinelli, David Booth, Steffan Bos, Dorothea Buck, Mariusz Butkiewicz, Elisabeth G. Celius, Manuel Comabella, Alastair Compston, Katrina Dedham, Chris Cotsapas, Sandra D’ Alfonso, Phil De Jager, Benedicte DuboisPierre Duquette, Bertrand Fontaine, Christiane Gasperi, Elia Gil, An Goris, Pierre Antoine Gourraud, Christiane Graetz, Alexandra Gyllenberg, Georgios Hadjigeorgiou, David Hafler, Deanna Hribko, Jonathan Haines, Hanne Harbo, Stephen Hauser, Shannon Warto, Clive Hawkins, Bernhard Hemmer, Roland Henry, Rogier Hintzen, Dana Horakova, Adrian Ivinson, Melissa Howard, Ilijas Jelcic, Belinda Kaskow, Jun Ichi Kira, Pavlina Kleinova, Ingrid Kockum, Karolina Kucerova, Christina Lill, Felix Luessi, Sunny Malhotra, Roland Martin, Filippo Martinelli, Takuya Matsushita, Cristin McCabe, Jacob McCauley, Julia Mescheriakkova, Mitja Mitrovic, Stine Marit Moen, Xavier Montalban, Mark Muhlau, Yuri Nakmura, Jorge Oksenberg, Tomas Olsson, Annette Oturai, Aarno Palotie, Nikolaos Patsopoulos, Jana Pavlicova, Peggy Pericak-Vance, Fredrik Piehl, Isabelle Rebeix, John Rioux, Janna Saarela, Stephen Sawcer, Finn Sellebjerg, Helle Bach Sondergaard, Per Soelberg Sorensen, Mireia Sospedra, Anne Spurkland, Graeme Stewart, Bruce Taylor, Andre Uitterlinden, Cornelia Van Duijn, Frauke Zipp

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


A recent study by Wang et al. (2016a) claims that the low-frequency variant NR1H3 p.Arg415Gln is sufficient to cause multiple sclerosis in certain individuals and determines a patient's likelihood of primary progressive disease. We sought to replicate this finding in the International MS Genetics Consortium (IMSGC) patient collection, which is 13-fold larger than the collection of Wang et al. (2016a), but we find no evidence that this variant is associated with either MS or disease subtype. Wang et al. (2016a) also report a common variant association in the region, which we show captures the association the IMSGC reported in 2013. Therefore, we conclude that the reported low-frequency association is a false positive, likely generated by insufficient sample size. The claim of NR1H3 mutations describing a Mendelian form of MS—of which no examples exist—can therefore not be substantiated by data. This Matters Arising paper is in response to Wang et al. (2016a), published in Neuron. See also the related Matters Arising paper by Minikel and MacArthur (2016) and the response by Wang et al. (2016b), published in this issue.

Original languageEnglish
Pages (from-to)333-335
Number of pages3
Issue number2
Publication statusPublished - Oct 19 2016

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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