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; Isabelle Arnulf; 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 EinenIsabelle Arnulf, 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

72 Citations (Scopus)

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
Journal	American Journal of Human Genetics
Volume	96
Issue number	1
Pages (from-to)	136-46
Number of pages	11
ISSN	0002-9297
DOIs	https://doi.org/10.1016/j.ajhg.2014.12.010
Publication status	Published - 8 Jan 2015

Keywords

Alleles
Asian Continental Ancestry Group
Case-Control Studies
Cohort Studies
European Continental Ancestry Group
Female
Genetic Loci
HLA-B Antigens
HLA-DP Antigens
HLA-DP beta-Chains
HLA-DQ alpha-Chains
HLA-DR Antigens
Haplotypes
Histocompatibility Antigens Class I
Humans
Influenza A Virus, H1N1 Subtype
Male
Narcolepsy
Risk Factors

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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), 136-46. https://doi.org/10.1016/j.ajhg.2014.12.010

Ollila, HM, 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, BR, Dong, XS, Yan, H, Hong, H, Coquillard, C, Mahlios, J, Jolanki, O, Einen, M, Arnulf, I, 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. 136-46. https://doi.org/10.1016/j.ajhg.2014.12.010

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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.",

keywords = "Alleles, Asian Continental Ancestry Group, Case-Control Studies, Cohort Studies, European Continental Ancestry Group, Female, Genetic Loci, HLA-B Antigens, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ alpha-Chains, HLA-DR Antigens, Haplotypes, Histocompatibility Antigens Class I, Humans, Influenza A Virus, H1N1 Subtype, Male, Narcolepsy, Risk Factors",

author = "Ollila, {Hanna M} and Jean-Marie Ravel and Fang Han and Juliette Faraco and Ling Lin and Xiuwen Zheng and Giuseppe Plazzi and Yves Dauvilliers and Fabio Pizza and Seung-Chul Hong 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 Isabelle Arnulf 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",

year = "2015",

month = jan,

day = "8",

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

language = "English",

volume = "96",

pages = "136--46",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

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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 - Arnulf, Isabelle

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.

KW - Alleles

KW - Asian Continental Ancestry Group

KW - Case-Control Studies

KW - Cohort Studies

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Loci

KW - HLA-B Antigens

KW - HLA-DP Antigens

KW - HLA-DP beta-Chains

KW - HLA-DQ alpha-Chains

KW - HLA-DR Antigens

KW - Haplotypes

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Influenza A Virus, H1N1 Subtype

KW - Male

KW - Narcolepsy

KW - Risk Factors

U2 - 10.1016/j.ajhg.2014.12.010

DO - 10.1016/j.ajhg.2014.12.010

M3 - Journal article

C2 - 25574827

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

Abstract

Keywords

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