HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy

Hanna M. Ollila; Jean Marie Ravel; Fang Han; Juliette Faraco; Ling Lin; Xiuwen Zheng; Giuseppe Plazzi; Yves Dauvilliers; Fabio Pizza; Seung Chul Hong; Poul Jennum; Stine Knudsen; Birgitte R. Kornum; Xiao Song Dong; Han Yan; Heeseung Hong; Cristin Coquillard; Joshua Mahlios; Otto Jolanki; Mali Einen; Sophie Lavault; Birgit Högl; Birgit Frauscher; Catherine Crowe; Markku Partinen; Yu Shu Huang; Patrice Bourgin; Outi Vaarala; Alex Désautels; Jacques Montplaisir; Steven J. Mack; Michael Mindrinos; Marcelo Fernandez-Vina; Emmanuel Mignot

doi:10.1016/j.ajhg.2014.12.010

HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy

Hanna M. Ollila
, Jean Marie Ravel
, Fang Han
, Juliette Faraco
, Ling Lin
, Xiuwen Zheng
, Giuseppe Plazzi
, Yves Dauvilliers
, Fabio Pizza
, Seung Chul Hong
, Poul Jennum
, Stine Knudsen
, Birgitte R. Kornum
, Xiao Song Dong
, Han Yan
, Heeseung Hong
, Cristin Coquillard
, Joshua Mahlios
, Otto Jolanki
, Mali Einen

Sophie Lavault, Birgit Högl, Birgit Frauscher, Catherine Crowe, Markku Partinen, Yu Shu Huang, Patrice Bourgin, Outi Vaarala, Alex Désautels, Jacques Montplaisir, Steven J. Mack, Michael Mindrinos, Marcelo Fernandez-Vina, Emmanuel Mignot

Department of Psychiatry

Stanford University
Peking University
University of Washington
University of Bologna
IRCCS Istituto delle Scienze Neurologiche di Bologna
CHU Montpellier
University of Copenhagen
University of Oslo
Centre National de Réferénce Narcolepsie et Hypersomnie
Innsbruck Medical University
Mater Private Hospital Dublin
Vitalmed Research Centre
University of Helsinki
Chang Gung Memorial Hospital
Department of Sleep Medicine, Strasbourg University Hospital, Strasbourg University
University of Montreal
UCSF Benioff Children's Hospital Oakland

Research output: Contribution to journal › Article › peer-review

134 Scopus citations

Abstract

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1^∗01:02-DQB1^∗06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1^∗01:03-DPB1^∗04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10^-6) and HLA-DPA1^∗01:03-DPB1^∗04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10^-4) and predisposing effects of HLA-DPB1^∗05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10^-05). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10^-17) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10^-5). HLA-class-II-independent associations with HLA-A^∗11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10^-4), HLA-B^∗35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10^-5), and HLA-B^∗51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10^-5) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

Original language	English
Pages (from-to)	136-146
Number of pages	11
Journal	American Journal of Human Genetics
Volume	96
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2014.12.010
State	Published - 8 Jan 2015

Bibliographical note

Publisher Copyright:
© 2015 The American Society of Human Genetics.

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10.1016/j.ajhg.2014.12.010

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Ollila, H. M., Ravel, J. M., Han, F., Faraco, J., Lin, L., Zheng, X., Plazzi, G., Dauvilliers, Y., Pizza, F., Hong, S. C., Jennum, P., Knudsen, S., Kornum, B. R., Dong, X. S., Yan, H., Hong, H., Coquillard, C., Mahlios, J., Jolanki, O., ... Mignot, E. (2015). HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy. American Journal of Human Genetics, 96(1), 136-146. https://doi.org/10.1016/j.ajhg.2014.12.010

@article{d593f753247b4e0f8109a36a0abaae79,

title = "HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy",

abstract = "Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1∗01:02-DQB1∗06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1∗01:03-DPB1∗04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10-6) and HLA-DPA1∗01:03-DPB1∗04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10-4) and predisposing effects of HLA-DPB1∗05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10-05). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10-17) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10-5). HLA-class-II-independent associations with HLA-A∗11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10-4), HLA-B∗35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10-5), and HLA-B∗51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10-5) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.",

author = "Ollila, \{Hanna M.\} and Ravel, \{Jean Marie\} and Fang Han and Juliette Faraco and Ling Lin and Xiuwen Zheng and Giuseppe Plazzi and Yves Dauvilliers and Fabio Pizza and Hong, \{Seung Chul\} and Poul Jennum and Stine Knudsen and Kornum, \{Birgitte R.\} and Dong, \{Xiao Song\} and Han Yan and Heeseung Hong and Cristin Coquillard and Joshua Mahlios and Otto Jolanki and Mali Einen and Sophie Lavault and Birgit H{\"o}gl and Birgit Frauscher and Catherine Crowe and Markku Partinen and Huang, \{Yu Shu\} and Patrice Bourgin and Outi Vaarala and Alex D{\'e}sautels and Jacques Montplaisir and Mack, \{Steven J.\} and Michael Mindrinos and Marcelo Fernandez-Vina and Emmanuel Mignot",

note = "Publisher Copyright: {\textcopyright} 2015 The American Society of Human Genetics.",

year = "2015",

month = jan,

day = "8",

doi = "10.1016/j.ajhg.2014.12.010",

language = "English",

volume = "96",

pages = "136--146",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

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Ollila, HM, Ravel, JM, Han, F, Faraco, J, Lin, L, Zheng, X, Plazzi, G, Dauvilliers, Y, Pizza, F, Hong, SC, Jennum, P, Knudsen, S, Kornum, BR, Dong, XS, Yan, H, Hong, H, Coquillard, C, Mahlios, J, Jolanki, O, Einen, M, Lavault, S, Högl, B, Frauscher, B, Crowe, C, Partinen, M, Huang, YS, Bourgin, P, Vaarala, O, Désautels, A, Montplaisir, J, Mack, SJ, Mindrinos, M, Fernandez-Vina, M & Mignot, E 2015, 'HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy', American Journal of Human Genetics, vol. 96, no. 1, pp. 136-146. https://doi.org/10.1016/j.ajhg.2014.12.010

TY - JOUR

T1 - HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy

AU - Ollila, Hanna M.

AU - Ravel, Jean Marie

AU - Han, Fang

AU - Faraco, Juliette

AU - Lin, Ling

AU - Zheng, Xiuwen

AU - Plazzi, Giuseppe

AU - Dauvilliers, Yves

AU - Pizza, Fabio

AU - Hong, Seung Chul

AU - Jennum, Poul

AU - Knudsen, Stine

AU - Kornum, Birgitte R.

AU - Dong, Xiao Song

AU - Yan, Han

AU - Hong, Heeseung

AU - Coquillard, Cristin

AU - Mahlios, Joshua

AU - Jolanki, Otto

AU - Einen, Mali

AU - Lavault, Sophie

AU - Högl, Birgit

AU - Frauscher, Birgit

AU - Crowe, Catherine

AU - Partinen, Markku

AU - Huang, Yu Shu

AU - Bourgin, Patrice

AU - Vaarala, Outi

AU - Désautels, Alex

AU - Montplaisir, Jacques

AU - Mack, Steven J.

AU - Mindrinos, Michael

AU - Fernandez-Vina, Marcelo

AU - Mignot, Emmanuel

PY - 2015/1/8

Y1 - 2015/1/8

N2 - Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1∗01:02-DQB1∗06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1∗01:03-DPB1∗04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10-6) and HLA-DPA1∗01:03-DPB1∗04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10-4) and predisposing effects of HLA-DPB1∗05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10-05). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10-17) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10-5). HLA-class-II-independent associations with HLA-A∗11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10-4), HLA-B∗35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10-5), and HLA-B∗51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10-5) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

AB - Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1∗01:02-DQB1∗06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1∗01:03-DPB1∗04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10-6) and HLA-DPA1∗01:03-DPB1∗04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10-4) and predisposing effects of HLA-DPB1∗05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10-05). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10-17) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10-5). HLA-class-II-independent associations with HLA-A∗11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10-4), HLA-B∗35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10-5), and HLA-B∗51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10-5) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

UR - https://www.scopus.com/pages/publications/84920733875

U2 - 10.1016/j.ajhg.2014.12.010

DO - 10.1016/j.ajhg.2014.12.010

M3 - Article

C2 - 25574827

AN - SCOPUS:84920733875

SN - 0002-9297

VL - 96

SP - 136

EP - 146

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

HLA-DPB1 and HLA class i confer risk of and protection from narcolepsy

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