Ollila, Hanna MHanna MOllilaSharon, EilonEilonSharonLin, LingLingLinSinnott-Armstrong, NasaNasaSinnott-ArmstrongAmbati, AdityaAdityaAmbatiYogeshwar, Selina MSelina MYogeshwarHillary, Ryan PRyan PHillaryJolanki, OttoOttoJolankiFaraco, JulietteJulietteFaracoEinen, MaliMaliEinenLuo, GuoGuoLuoZhang, JingJingZhangHan, FangFangHanYan, HanHanYanDong, Xiao SongXiao SongDongLi, JingJingLiZhang, JunJunZhangHong, Seung-ChulSeung-ChulHongKim, Tae WonTae WonKimDauvilliers, YvesYvesDauvilliersBarateau, LucieLucieBarateauLammers, Gert JanGert JanLammersFronczek, RolfRolfFronczekMayer, GeertGeertMayerSantamaria, JoanJoanSantamariaArnulf, IsabelleIsabelleArnulfKnudsen-Heier, StineStineKnudsen-HeierBredahl, May Kristin LyamouriMay Kristin LyamouriBredahlThorsby, Per MedbøePer MedbøeThorsbyPlazzi, GiuseppeGiuseppePlazziPizza, FabioFabioPizzaMoresco, MonicaMonicaMorescoCrowe, CatherineCatherineCroweVan den Eeden, Stephen KStephen KVan den EedenLecendreux, MichelMichelLecendreuxBourgin, PatricePatriceBourginKanbayashi, TakashiTakashiKanbayashiMartínez-Orozco, Francisco JFrancisco JMartínez-OrozcoPeraita-Adrados, RosaRosaPeraita-AdradosBenetó, AntonioAntonioBenetóMontplaisir, JacquesJacquesMontplaisirDesautels, AlexAlexDesautelsHuang, Yu-ShuYu-ShuHuangJennum, PoulPoulJennumNevsimalova, SonaSonaNevsimalovaKemlink, DavidDavidKemlinkIranzo, AlexAlexIranzoOvereem, SebastiaanSebastiaanOvereemWierzbicka, AleksandraAleksandraWierzbickaGeisler, PeterPeterGeislerSonka, KarelKarelSonkaHonda, MakotoMakotoHondaHögl, BirgitBirgitHöglStefani, AmbraAmbraStefaniCoelho, Fernando MorgadinhoFernando MorgadinhoCoelhoMantovani, VilmaVilmaMantovaniFeketeova, EvaEvaFeketeovaWadelius, MiaMiaWadeliusEriksson, NiclasNiclasErikssonSmedje, HansHansSmedjeHallberg, PärPärHallbergHesla, Per EgilPer EgilHeslaRye, DavidDavidRyePelin, ZerrinZerrinPelinFerini-Strambi, LuigiLuigiFerini-StrambiBassetti, Claudio L. A.Claudio L. A.BassettiMathis, JohannesJohannesMathisKhatami, RaminRaminKhatamiAran, AdiAdiAranNampoothiri, SheelaSheelaNampoothiriOlsson, TomasTomasOlssonKockum, IngridIngridKockumPartinen, MarkkuMarkkuPartinenPerola, MarkusMarkusPerolaKornum, Birgitte RBirgitte RKornumRueger, SinaSinaRuegerWinkelmann, JulianeJulianeWinkelmannMiyagawa, TakuTakuMiyagawaToyoda, HiromiHiromiToyodaKhor, Seik-SoonSeik-SoonKhorShimada, MihokoMihokoShimadaTokunaga, KatsushiKatsushiTokunagaRivas, ManuelManuelRivasPritchard, Jonathan KJonathan KPritchardRisch, NeilNeilRischKutalik, ZoltanZoltanKutalikO'Hara, RuthRuthO'HaraHallmayer, JoachimJoachimHallmayerYe, Chun JimmieChun JimmieYeMignot, Emmanuel JEmmanuel JMignot2024-10-252024-10-252023-05-15https://boris-portal.unibe.ch/handle/20.500.12422/167164Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.en600 - Technology::610 - Medicine & healtharticle10.48350/1826103718866310.1038/s41467-023-36120-z