Xie, JingyuanJingyuanXieLiu, LiliLiliLiuMladkova, NikolNikolMladkovaLi, YifuYifuLiRen, HongHongRenWang, WeimingWeimingWangCui, ZhaoZhaoCuiLin, LiLiLinHu, XiaofanXiaofanHuYu, XialianXialianYuXu, JingJingXuLiu, GangGangLiuCaliskan, YasarYasarCaliskanSidore, CarloCarloSidoreBalderes, OliviaOliviaBalderesRosen, RaphaelRaphaelRosenBodria, MonicaMonicaBodriaZanoni, FrancescaFrancescaZanoniZhang, YunYunZhangKrithivasan, PriyaPriyaKrithivasanMehl, KarlaKarlaMehlMarasa, MaddalenaMaddalenaMarasaKhan, AtlasAtlasKhanOzay, FatihFatihOzayCanetta, PietroPietroCanettaBomback, AndrewAndrewBombackAppel, GeraldGeraldAppelSanna-Cherchi, SimoneSimoneSanna-CherchiSampson, MatthewMatthewSampsonMariani, LauraLauraMarianiPerkowska-Ptasinska, AgnieszkaAgnieszkaPerkowska-PtasinskaDurlik, MagdalenaMagdalenaDurlikMucha, KrzysztofKrzysztofMuchaMoszczuk, BarbaraBarbaraMoszczukForoncewicz, BartoszBartoszForoncewiczPączek, LeszekLeszekPączekHabura, IreneuszIreneuszHaburaArs, ElisabetElisabetArsBallarin, JoseJoseBallarinMani, Laila-YasminLaila-YasminMani0000-0002-4693-7814Vogt, BrunoBrunoVogtOzturk, SavasSavasOzturkYildiz, AbdülmecitAbdülmecitYildizNurhan, SeyahiSeyahiNurhanArikan, HakkiHakkiArikanKoc, MehmetMehmetKocBasturk, TanerTanerBasturkKarahan, GoncaGoncaKarahanAkgul, SebahatSebahatAkgulSever, MehmetMehmetSeverZhang, DanDanZhangSantoro, DomenicoDomenicoSantoroBonomini, MarioMarioBonominiLondrino, FrancescoFrancescoLondrinoGesualdo, LoretoLoretoGesualdoReiterova, JanaJanaReiterovaTesar, VladimirVladimirTesarIzzi, ClaudiaClaudiaIzziSavoldi, SilvanaSilvanaSavoldiSpotti, DonatellaDonatellaSpottiMarcantoni, CarmelitaCarmelitaMarcantoniMessa, PiergiorgioPiergiorgioMessaGalliani, MarcoMarcoGallianiRoccatello, DarioDarioRoccatelloGranata, SimonaSimonaGranataZaza, GianluigiGianluigiZazaLugani, FrancescaFrancescaLuganiGhiggeri, Gian MarcoGian MarcoGhiggeriPisani, IsabellaIsabellaPisaniAllegri, LandinoLandinoAllegriSprangers, BenBenSprangersPark, Jin-HoJin-HoParkCho, BeLongBeLongChoKim, Yon SuYon SuKimKim, Dong KiDong KiKimSuzuki, HitoshiHitoshiSuzukiAmoroso, AntonioAntonioAmorosoCattran, DanielDanielCattranFervenza, FernandoFernandoFervenzaPani, AntonelloAntonelloPaniHamilton, PatrickPatrickHamiltonHarris, ShellyShellyHarrisGupta, SanjanaSanjanaGuptaCheshire, ChrisChrisCheshireDufek, StephanieStephanieDufekIssler, NaomiNaomiIsslerPepper, RuthRuthPepperConnolly, JohnJohnConnollyPowis, StephenStephenPowisBockenhauer, DetlefDetlefBockenhauerStanescu, HoriaHoriaStanescuAshman, NeilNeilAshmanLoos, RuthRuthLoosKenny, EimearEimearKennyWuttke, MatthiasMatthiasWuttkeEckardt, Kai-UweKai-UweEckardtKöttgen, AnnaAnnaKöttgenHofstra, JuliaJuliaHofstraCoenen, MariekeMariekeCoenenKiemeney, LambertusLambertusKiemeneyAkilesh, ShreeramShreeramAkileshKretzler, MatthiasMatthiasKretzlerBeck, LawrenceLawrenceBeckStengel, BenedicteBenedicteStengelDebiec, HannaHannaDebiecRonco, PierrePierreRoncoWetzels, JackJackWetzelsZoledziewska, MagdalenaMagdalenaZoledziewskaCucca, FrancescoFrancescoCuccaIonita-Laza, IulianaIulianaIonita-LazaLee, HajeongHajeongLeeHoxha, ElionElionHoxhaStahl, RolfRolfStahlBrenchley, PaulPaulBrenchleyScolari, FrancescoFrancescoScolariZhao, Ming-HuiMing-HuiZhaoGharavi, AliAliGharaviKleta, RobertRobertKletaChen, NanNanChenKiryluk, KrzysztofKrzysztofKiryluk2024-09-022024-09-022020-03-30https://boris-portal.unibe.ch/handle/20.500.12422/40442Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.en600 - Technology::610 - Medicine & healtharticle10.48350/1530483223124410.1038/s41467-020-15383-w