Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic

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Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7×10⁻⁹ OR 0.77), ZNF365 (rs10995245 max P = 1.2×10⁻¹¹ OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2×10⁻⁹ OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10⁻⁹ beta −1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8×10⁻¹⁰ OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

Vyšlo v časopise: Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic. PLoS Genet 9(10): e32767. doi:10.1371/journal.pgen.1003880
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003880

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Zdroje

1. MignotE, LinL, RogersW, HondaY, QiuX, et al. (2001) Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. American journal of human genetics 68: 686–699.

2. HongSC, LinL, LoB, JeongJH, ShinYK, et al. (2007) DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans. Human immunology 68: 59–68.

3. HanF, LinL, LiJ, DongSX, AnP, et al. (2012) HLA-DQ association and allele competition in Chinese narcolepsy. Tissue Antigens 80: 328–335.

4. HorH, KutalikZ, DauvilliersY, ValsesiaA, LammersGJ, et al. (2010) Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nature genetics 42: 786–789.

5. PelinZ, GuilleminaultC, RischN, GrumetFC, MignotE (1998) HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. US Modafinil in Narcolepsy Multicenter Study Group. Tissue Antigens 51: 96–100.

6. HallmayerJ, FaracoJ, LinL, HesselsonS, WinkelmannJ, et al. (2009) Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet 41: 708–711.

7. KornumBR, KawashimaM, FaracoJ, LinL, RicoTJ, et al. (2011) Common variants in P2RY11 are associated with narcolepsy. Nat Genet 43: 66–71.

8. FaracoJ, LinL, KornumBR, KennyEE, TrynkaG, et al. (2013) ImmunoChip study implicates antigen presentation to T cells in narcolepsy. PLoS Genet 9: e1003270.

9. HanF, LinL, WarbySC, FaracoJ, LiJ, et al. (2011) Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann Neurol 70: 410–417.

10. AranA, LinL, NevsimalovaS, PlazziG, HongSC, et al. (2009) Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep 32: 979–983.

11. LongstrethWTJr, TonTG, KoepsellTD (2009) Narcolepsy and streptococcal infections. Sleep 32: 1548.

12. DauvilliersY, MontplaisirJ, CochenV, DesautelsA, EinenM, et al. (2010) Post-H1N1 narcolepsy-cataplexy. Sleep 33: 1428–1430.

13. MeeyaiA, CooperBS, CokerR (2013) Analysis of 2009 pandemic influenza A/H1N1 outcomes in 19 European countries: association with completeness of national strategic plans. BMJ open 3: e002253.

14. NohynekH, JokinenJ, PartinenM, VaaralaO, KirjavainenT, et al. (2012) AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One 7: e33536.

15. MillerE, AndrewsN, StellitanoL, StoweJ, WinstoneAM, et al. (2013) Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. BMJ 346: f794.

16. SzakacsA, DarinN, HallbookT (2013) Increased childhood incidence of narcolepsy in western Sweden after H1N1 influenza vaccination. Neurology 80: 1315–1321.

17. WijnansL, LecomteC, de VriesC, WeibelD, SammonC, et al. (2013) The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns. Vaccine 31: 1246–1254.

18. HanF, LinL, LiJ, DongXS, MignotE (2012) Decreased incidence of childhood narcolepsy 2 years after the 2009 H1N1 winter flu pandemic. Ann Neurol E-pub ahead of print. doi: 10.1002/ana.23799

19. PartinenM, Saarenpaa-HeikkilaO, IlveskoskiI, HublinC, LinnaM, et al. (2012) Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland. PLoS One 7: e33723.

20. LanL, LuW, LiS, YinJ, XieJ, et al. (2011) Evolutionary characteristics of swine-origin H1N1 influenza virus that infected humans from sporadic to pandemic. Journal of Public Health and Epidemiology 3: 254–270.

21. HanF, LinL, LiJ, AranA, DongSX, et al. (2011) Presentations of primary hypersomnia in Chinese children. Sleep 34: 627–632.

22. HanF, LinL, LiJ, AranA, DongSX, et al. (2012) TCRA, P2RY11, and CPT1B/CHKB associations in Chinese narcolepsy. Sleep Med 13: 269–272.

23. WinkelmannJ, LinL, SchormairB, KornumBR, FaracoJ, et al. (2012) Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet 21: 2205–2210.

24. HirotaT, TakahashiA, KuboM, TsunodaT, TomitaK, et al. (2012) Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 44: 1222–1226.

25. WatermanM, XuW, StempakJM, MilgromR, BernsteinCN, et al. (2011) Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis. Inflamm Bowel Dis 17: 1936–1942.

26. Huertas-VazquezA, NelsonCP, GuoX, ReinierK, Uy-EvanadoA, et al. (2013) Novel Loci associated with increased risk of sudden cardiac death in the context of coronary artery disease. PLoS One 8: e59905.

27. CouchFJ, GaudetMM, AntoniouAC, RamusSJ, KuchenbaeckerKB, et al. (2012) Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 21: 645–657.

28. HarituniansT, JonesMR, McGovernDP, ShihDQ, BarrettRJ, et al. (2011) Variants in ZNF365 isoform D are associated with Crohn's disease. Gut 60: 1060–1067.

29. BegueB, VerdierJ, Rieux-LaucatF, GouletO, MoraliA, et al. (2011) Defective IL10 signaling defining a subgroup of patients with inflammatory bowel disease. Am J Gastroenterol 106: 1544–1555.

30. MaoH, YangW, LeePP, HoMH, YangJ, et al. (2012) Exome sequencing identifies novel compound heterozygous mutations of IL-10 receptor 1 in neonatal-onset Crohn's disease. Genes Immun 13: 437–442.

31. KalinkeU, PrinzM (2012) Endogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS. Immunol Cell Biol 90: 505–509.

32. LucaG, Haba-RubioJ, DauvilliersY, LammersGJ, OvereemS, et al. (2013) Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. J Sleep Res 22: 482–495.

33. PelinZ, BozluolcayM, KaynakD, KaynakH (2002) Childhood onset of narcolepsy-cataplexy syndrome in Turkey: clinical and genetic study. Turk J Pediatr 44: 321–325.

34. FraserC, DonnellyCA, CauchemezS, HanageWP, Van KerkhoveMD, et al. (2009) Pandemic potential of a strain of influenza A (H1N1): early findings. Science 324: 1557–1561.

35. PurcellS, NealeB, Todd-BrownK, ThomasL, FerreiraMA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. American journal of human genetics 81: 559–575.

36. KangHM, SulJH, ServiceSK, ZaitlenNA, KongSY, et al. (2010) Variance component model to account for sample structure in genome-wide association studies. Nature genetics 42: 348–354.

37. AulchenkoYS, RipkeS, IsaacsA, van DuijnCM (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23: 1294–1296.

38. Team RDC (2008) R: A language and environment for statistical computing. Computing RFfS, editor. Vienna, Austria.

39. BrowningSR, BrowningBL (2007) Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. American journal of human genetics 81: 1084–1097.

40. PruimRJ, WelchRP, SannaS, TeslovichTM, ChinesPS, et al. (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26: 2336–2337.

41. ZhengX, ShenJ, CoxC, WakefieldJC, EhmMG, et al. (2013) HIBAG-HLA genotype imputation with attribute bagging. Pharmacogenomics J E-pub ahead of print. doi: 10.1038/tpj.2013.18

42. HeiAL, LiW, DengZH, HeJ, JinWM, et al. (2009) Analysis of high-resolution HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor-recipient confirmatory typings. International journal of immunogenetics 36: 275–282.

43. HollenbachJA, MackSJ, ThomsonG, GourraudPA (2012) Analytical methods for disease association studies with immunogenetic data. Methods in molecular biology 882: 245–266.