HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy
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HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. / Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang; Faraco, Juliette; Lin, Ling; Zheng, Xiuwen; Plazzi, Giuseppe; Dauvilliers, Yves; Pizza, Fabio; Hong, Seung-Chul; Jennum, Poul; Knudsen, Stine; Kornum, Birgitte R; Dong, Xiao Song; Yan, Han; Hong, Heeseung; Coquillard, Cristin; Mahlios, Joshua; Jolanki, Otto; Einen, Mali; Arnulf, Isabelle; Lavault, Sophie; Högl, Birgit; Frauscher, Birgit; Crowe, Catherine; Partinen, Markku; Huang, Yu Shu; Bourgin, Patrice; Vaarala, Outi; Désautels, Alex; Montplaisir, Jacques; Mack, Steven J; Mindrinos, Michael; Fernandez-Vina, Marcelo; Mignot, Emmanuel.
In: American Journal of Human Genetics, Vol. 96, No. 1, 08.01.2015, p. 136-46.Research output: Contribution to journal › Journal article › Research › peer-review
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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
N1 - Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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
VL - 96
SP - 136
EP - 146
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -
ID: 162677062