PMID- 27764667 OWN - NLM STAT- MEDLINE DCOM- 20171026 LR - 20181113 IS - 1097-4199 (Electronic) IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 92 IP - 2 DP - 2016 Oct 19 TI - NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk. PG - 333-335 LID - S0896-6273(16)30694-8 [pii] LID - 10.1016/j.neuron.2016.09.052 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. CN - International Multiple Sclerosis Genetics Consortium. Electronic address: cotsapas@broadinstitute.org CN - International Multiple Sclerosis Genetics Consortium LA - eng GR - R01 NS049477/NS/NINDS NIH HHS/United States GR - R01 NS088155/NS/NINDS NIH HHS/United States PT - Journal Article PL - United States TA - Neuron JT - Neuron JID - 8809320 SB - IM EIN - Neuron. 2016 Nov 23;92(4):929. PMID: 27883903 MH - Humans MH - Multiple Sclerosis/*genetics MH - Mutation MH - *Polymorphism, Single Nucleotide MH - Risk PMC - PMC5641967 MID - NIHMS910422 FIR - Antel, Jack IR - Antel J FIR - Ban, Maria IR - Ban M FIR - Baranzini, Sergio IR - Baranzini S FIR - Barcellos, Lisa IR - Barcellos L FIR - Barizzone, Nadia IR - Barizzone N FIR - Beecham, Ashley IR - Beecham A FIR - Berge, Tone IR - Berge T FIR - Bernardinelli, Luisa IR - Bernardinelli L FIR - Booth, David IR - Booth D FIR - Bos, Steffan IR - Bos S FIR - Buck, Dorothea IR - Buck D FIR - Butkiewicz, Mariusz IR - Butkiewicz M FIR - Celius, Elisabeth G IR - Celius EG FIR - Comabella, Manuel IR - Comabella M FIR - Compston, Alastair IR - Compston A FIR - Dedham, Katrina IR - Dedham K FIR - Cotsapas, Chris IR - Cotsapas C FIR - D' Alfonso, Sandra IR - D' Alfonso S FIR - De Jager, Phil IR - De Jager P FIR - Dubois, Benedicte IR - Dubois B FIR - Duquette, Pierre IR - Duquette P FIR - Fontaine, Bertrand IR - Fontaine B FIR - Gasperi, Christiane IR - Gasperi C FIR - Gil, Elia IR - Gil E FIR - Goris, An IR - Goris A FIR - Gourraud, Pierre Antoine IR - Gourraud PA FIR - Graetz, Christiane IR - Graetz C FIR - Gyllenberg, Alexandra IR - Gyllenberg A FIR - Hadjigeorgiou, Georgios IR - Hadjigeorgiou G FIR - Hafler, David IR - Hafler D FIR - Hribko, Deanna IR - Hribko D FIR - Haines, Jonathan IR - Haines J FIR - Harbo, Hanne IR - Harbo H FIR - Hauser, Stephen IR - Hauser S FIR - Warto, Shannon IR - Warto S FIR - Hawkins, Clive IR - Hawkins C FIR - Hemmer, Bernhard IR - Hemmer B FIR - Henry, Roland IR - Henry R FIR - Hintzen, Rogier IR - Hintzen R FIR - Horakova, Dana IR - Horakova D FIR - Ivinson, Adrian IR - Ivinson A FIR - Howard, Melissa IR - Howard M FIR - Jelcic, Ilijas IR - Jelcic I FIR - Kaskow, Belinda IR - Kaskow B FIR - Kira, Jun-Ichi IR - Kira JI FIR - Kleinova, Pavlina IR - Kleinova P FIR - Kockum, Ingrid IR - Kockum I FIR - Kucerova, Karolina IR - Kucerova K FIR - Lill, Christina IR - Lill C FIR - Luessi, Felix IR - Luessi F FIR - Malhotra, Sunny IR - Malhotra S FIR - Martin, Roland IR - Martin R FIR - Martinelli, Filippo IR - Martinelli F FIR - Matsushita, Takuya IR - Matsushita T FIR - McCabe, Cristin IR - McCabe C FIR - McCauley, Jacob IR - McCauley J FIR - Mescheriakkova, Julia IR - Mescheriakkova J FIR - Mitrovic, Mitja IR - Mitrovic M FIR - Moen, Stine-Marit IR - Moen SM FIR - Montalban, Xavier IR - Montalban X FIR - Muhlau, Mark IR - Muhlau M FIR - Nakmura, Yuri IR - Nakmura Y FIR - Oksenberg, Jorge IR - Oksenberg J FIR - Olsson, Tomas IR - Olsson T FIR - Oturai, Annette IR - Oturai A FIR - Palotie, Aarno IR - Palotie A FIR - Patsopoulos, Nikolaos IR - Patsopoulos N FIR - Pavlicova, Jana IR - Pavlicova J FIR - Pericak-Vance, Peggy IR - Pericak-Vance P FIR - Piehl, Fredrik IR - Piehl F FIR - Rebeix, Isabelle IR - Rebeix I FIR - Rioux, John IR - Rioux J FIR - Saarela, Janna IR - Saarela J FIR - Sawcer, Stephen IR - Sawcer S FIR - Sellebjerg, Finn IR - Sellebjerg F FIR - Sondergaard, Helle Bach IR - Sondergaard HB FIR - Sorensen, Per Soelberg IR - Sorensen PS FIR - Sospedra, Mireia IR - Sospedra M FIR - Spurkland, Anne IR - Spurkland A FIR - Stewart, Graeme IR - Stewart G FIR - Taylor, Bruce IR - Taylor B FIR - Uitterlinden, Andre IR - Uitterlinden A FIR - Van Duijn, Cornelia IR - Van Duijn C FIR - Zipp, Frauke IR - Zipp F EDAT- 2016/10/21 06:00 MHDA- 2017/10/27 06:00 PMCR- 2017/10/16 CRDT- 2016/10/21 06:00 PHST- 2016/06/30 00:00 [received] PHST- 2016/09/16 00:00 [revised] PHST- 2016/09/21 00:00 [accepted] PHST- 2016/10/21 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] PHST- 2016/10/21 06:00 [entrez] PHST- 2017/10/16 00:00 [pmc-release] AID - S0896-6273(16)30694-8 [pii] AID - 10.1016/j.neuron.2016.09.052 [doi] PST - ppublish SO - Neuron. 2016 Oct 19;92(2):333-335. doi: 10.1016/j.neuron.2016.09.052.