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 Dubois; Pierre 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

doi:10.1016/j.neuron.2016.09.052

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

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

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.

Lingua originale	Inglese
pagine (da-a)	333-335
Numero di pagine	3
Rivista	Neuron
Volume	92
Numero di pubblicazione	2
DOI	https://doi.org/10.1016/j.neuron.2016.09.052
Stato di pubblicazione	Pubblicato - 19 ott 2016

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Antel, J., Ban, M., Baranzini, S., Barcellos, L., Barizzone, N., Beecham, A., Berge, T., Bernardinelli, L., Booth, D., Bos, S., Buck, D., Butkiewicz, M., Celius, E. G., Comabella, M., Compston, A., Dedham, K., Cotsapas, C., D’ Alfonso, S., De Jager, P., ... Zipp, F. (2016). NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk. Neuron, 92(2), 333-335. https://doi.org/10.1016/j.neuron.2016.09.052

@article{28dc97a63085418b8f40dffceba92d3a,

title = "NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk",

abstract = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = oct,

day = "19",

doi = "10.1016/j.neuron.2016.09.052",

language = "English",

volume = "92",

pages = "333--335",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

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Antel, J, Ban, M, Baranzini, S, Barcellos, L, Barizzone, N, Beecham, A, Berge, T, Bernardinelli, L, Booth, D, Bos, S, Buck, D, Butkiewicz, M, Celius, EG, Comabella, M, Compston, A, Dedham, K, Cotsapas, C, D’ Alfonso, S, De Jager, P, Dubois, B, Duquette, P, Fontaine, B, Gasperi, C, Gil, E, Goris, A, Gourraud, PA, Graetz, C, Gyllenberg, A, Hadjigeorgiou, G, Hafler, D, Hribko, D, Haines, J, Harbo, H, Hauser, S, Warto, S, Hawkins, C, Hemmer, B, Henry, R, Hintzen, R, Horakova, D, Ivinson, A, Howard, M, Jelcic, I, Kaskow, B, Kira, JI, Kleinova, P, Kockum, I, Kucerova, K, Lill, C, Luessi, F, Malhotra, S, Martin, R, Martinelli, F, Matsushita, T, McCabe, C, McCauley, J, Mescheriakkova, J, Mitrovic, M, Moen, SM, Montalban, X, Muhlau, M, Nakmura, Y, Oksenberg, J, Olsson, T, Oturai, A, Palotie, A, Patsopoulos, N, Pavlicova, J, Pericak-Vance, P, Piehl, F, Rebeix, I, Rioux, J, Saarela, J, Sawcer, S, Sellebjerg, F, Sondergaard, HB, Sorensen, PS, Sospedra, M, Spurkland, A, Stewart, G, Taylor, B, Uitterlinden, A, Van Duijn, C & Zipp, F 2016, 'NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk', Neuron, vol. 92, n. 2, pagg. 333-335. https://doi.org/10.1016/j.neuron.2016.09.052

TY - JOUR

T1 - NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk

AU - Antel, Jack

AU - Ban, Maria

AU - Baranzini, Sergio

AU - Barcellos, Lisa

AU - Barizzone, Nadia

AU - Beecham, Ashley

AU - Berge, Tone

AU - Bernardinelli, Luisa

AU - Booth, David

AU - Bos, Steffan

AU - Buck, Dorothea

AU - Butkiewicz, Mariusz

AU - Celius, Elisabeth G.

AU - Comabella, Manuel

AU - Compston, Alastair

AU - Dedham, Katrina

AU - Cotsapas, Chris

AU - D’ Alfonso, Sandra

AU - De Jager, Phil

AU - Dubois, Benedicte

AU - Duquette, Pierre

AU - Fontaine, Bertrand

AU - Gasperi, Christiane

AU - Gil, Elia

AU - Goris, An

AU - Gourraud, Pierre Antoine

AU - Graetz, Christiane

AU - Gyllenberg, Alexandra

AU - Hadjigeorgiou, Georgios

AU - Hafler, David

AU - Hribko, Deanna

AU - Haines, Jonathan

AU - Harbo, Hanne

AU - Hauser, Stephen

AU - Warto, Shannon

AU - Hawkins, Clive

AU - Hemmer, Bernhard

AU - Henry, Roland

AU - Hintzen, Rogier

AU - Horakova, Dana

AU - Ivinson, Adrian

AU - Howard, Melissa

AU - Jelcic, Ilijas

AU - Kaskow, Belinda

AU - Kira, Jun Ichi

AU - Kleinova, Pavlina

AU - Kockum, Ingrid

AU - Kucerova, Karolina

AU - Lill, Christina

AU - Luessi, Felix

AU - Malhotra, Sunny

AU - Martin, Roland

AU - Martinelli, Filippo

AU - Matsushita, Takuya

AU - McCabe, Cristin

AU - McCauley, Jacob

AU - Mescheriakkova, Julia

AU - Mitrovic, Mitja

AU - Moen, Stine Marit

AU - Montalban, Xavier

AU - Muhlau, Mark

AU - Nakmura, Yuri

AU - Oksenberg, Jorge

AU - Olsson, Tomas

AU - Oturai, Annette

AU - Palotie, Aarno

AU - Patsopoulos, Nikolaos

AU - Pavlicova, Jana

AU - Pericak-Vance, Peggy

AU - Piehl, Fredrik

AU - Rebeix, Isabelle

AU - Rioux, John

AU - Saarela, Janna

AU - Sawcer, Stephen

AU - Sellebjerg, Finn

AU - Sondergaard, Helle Bach

AU - Sorensen, Per Soelberg

AU - Sospedra, Mireia

AU - Spurkland, Anne

AU - Stewart, Graeme

AU - Taylor, Bruce

AU - Uitterlinden, Andre

AU - Van Duijn, Cornelia

AU - Zipp, Frauke

PY - 2016/10/19

Y1 - 2016/10/19

N2 - 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.

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.

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U2 - 10.1016/j.neuron.2016.09.052

DO - 10.1016/j.neuron.2016.09.052

M3 - Article

SN - 0896-6273

VL - 92

SP - 333

EP - 335

JO - Neuron

JF - Neuron

IS - 2

ER -

NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk

Abstract

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