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A catalog of genetic loci associated with kidney function from analyses of a million individuals.

Matthias WuttkeYong LiMan LiKarsten B SieberMary F FeitosaMathias GorskiAdrienne TinLihua WangAudrey Y ChuAnselm HoppmannHolger KirstenAyush GiriJin-Fang ChaiGardar SveinbjornssonBamidele O TayoTeresa NutileChristian FuchsbergerJonathan MartenMassimiliano CoccaSahar GhasemiYizhe XuKatrin HornDamia NocePeter J van der MostSanaz SedaghatZhi YuMasato AkiyamaSaima AfaqTarunveer S AhluwaliaPeter AlmgrenNajaf AminJohan ÄrnlövStephan J L BakkerNisha BansalDaniela BaptistaSven BergmannMary L BiggsGinevra BiinoMichael BoehnkeEric BoerwinkleMathilde BoisselErwin P BottingerThibaud S BoutinHermann BrennerMarco BrumatRalph BurkhardtAdam S ButterworthEric CampanaArchie I CampbellHarry CampbellMickaël CanouilRobert J CarrollEulalia CatamoJohn C ChambersMiao-Ling CheeMiao-Li CheeXu ChenChing-Yu ChengYurong ChengKaare ChristensenRenata CifkovaMarina CiulloMaria Pina ConcasJames P CookJosef CoreshTanguy CorreCinzia Felicita SalaDaniele CusiJohn DaneshE Warwick DawMartin H de BorstAlessandro De GrandiRenée de MutsertAiko P J de VriesFrauke DegenhardtGraciela DelgadoAyse DemirkanEmanuele Di AngelantonioKatalin DittrichJasmin DiversRajkumar DorajooKai-Uwe EckardtGeorg B EhretPaul ElliottKarlhans EndlichMichele K EvansJanine F FelixValencia Hui Xian FooOscar H FrancoAndre FrankeBarry I FreedmanSandra Freitag-WolfYechiel FriedlanderPhillippe FroguelRon T GansevoortHe GaoPaolo GaspariniJ Michael GazianoVilmantas GiedraitisChristian GiegerGiorgia GirottoFranco GiulianiniMartin GögeleScott D GordonDaníel F GuðbjartssonVilmundur G GudnasonToomas HallerPavel HametTamara B HarrisCatharina A HartmanCaroline HaywardJacklyn N HellwegeChew-Kiat HengAndrew A HicksEdith HoferWei HuangNina Hutri-KähönenShih-Jen HwangMohammad Arfan IkramOlafur S IndridasonErik IngelssonMarcus IsingVincent W V JaddoeJohanna JakobsdottirJost Bruno JonasPeter K JoshiNavya Shilpa JosyulaBettina JungMika KähönenYoichiro KamataniCandace M KammererMasahiro KanaiMika KastarinenShona M KerrChiea Chuen KhorWieland KiessMarcus Edi KleberWolfgang KoenigJaspal S KoonerAntje KörnerPeter KovacsAldi T KrajaAlena KrajcoviechovaHolly KramerBernhard K KrämerFlorian KronenbergMichiaki KuboBrigitte KühnelMikko KuokkanenJohanna KuusistoMartina La BiancaMarkku LaaksoLeslie A LangeCarl D LangefeldJeannette Jen-Mai LeeBenjamin LehneTerho LehtimäkiWolfgang Liebnull nullSu-Chi LimLars LindCecilia M LindgrenJun LiuJian-Jun LiuMarkus LoefflerRuth J F LoosSusanne LucaeMary Ann LukasLeo-Pekka LyytikainenReedik MägiPatrik K E MagnussonAnubha MahajanNicholas G MartinJade MartinsWinfried MärzDeborah MascalzoniKoichi MatsudaChrista MeisingerThomas MeitingerOlle MelanderAndres MetspaluEvgenia K MikaelsdottirYuri MilaneschiKozeta MilikuPashupati P Mishranull nullKaren L MohlkeNina MononenGrant W MontgomeryDennis O Mook-KanamoriJosyf C MychaleckyiGirish N NadkarniMike A NallsMatthias NauckKjell NikusBoting NingIlja Maria NolteRaymond NoordamJeffrey O'ConnellMichelle L O'DonoghueIsleifur OlafssonAlbertine J OldehinkelMarju Orho-MelanderWillem H OuwehandSandosh PadmanabhanNicholette D PalmerRunolfur PalssonBrenda W J H PenninxThomas PerlsMarkus PerolaMario PirastuNicola PirastuGiorgio PistisAnna I PodgornaiaOzren PolasekBelen PonteDavid J PorteousTanja PoulainPeter P PramstallerMichael H PreussBram P PrinsMichael A ProvinceTon J RabelinkLaura M RaffieldOlli T RaitakariDermot F ReillyRainer RettigMyriam RheinbergerKenneth M RicePaul M RidkerFernando RivadeneiraFederica RizziDavid J RobertsAntonietta RobinoPeter RossingIgor RudanRico RueediDaniela RuggieroKathleen A RyanYasaman SabaSabanayagam CharumathiVeikko V SalomaaMirna AndelicKai-Uwe SaumHelena SchmidtReinhold SchmidtBen SchöttkerChristina-Alexandra SchulzNicole SchupfChristian M ShafferYuan ShiAlbert Vernon SmithBlair H SmithNicole SoranzoCassandra N SpracklenKonstantin StrauchHeather M StringhamMichael StumvollPer O SvenssonSilke SzymczakE-Shyong TaiSalman M TajuddinNicholas Y Q TanKent D TaylorAndrej TerenYih-Chung ThamJoachim ThieryChris H L ThioHauke ThomsenGudmar ThorleifssonDaniela TonioloAnke TönjesJohanne TremblayJoanna TzoulakiAndré G UitterlindenSimona VaccargiuRob M van DamPim van der HarstCornelia M van DuijnDigna R Velez EdwardNiek VerweijSuzanne VogelezangUwe VölkerPeter VollenweiderGerard WaeberMelanie WaldenbergerLars WallentinYa-Xing WangChaolong WangDawn M WaterworthWen Bin WeiHarvey WhiteJohn B WhitfieldSarah H WildJames F WilsonMary K WojczynskiCharlene WongTien-Yin WongLiang XuQiong YangMasayuki YasudaLaura M Yerges-ArmstrongWeihua ZhangAlan B ZondermanJerome I RotterMurielle BochudBruce M PsatyVeronique VitartJames G WilsonAbbas DehghanAfshin ParsaDaniel I ChasmanKevin HoAndrew P MorrisOlivier DevuystShreeram AkileshSarah A PendergrassXueling S SimCarsten A BögerYukinori OkadaTodd L EdwardsHarold SniederKári StefánssonAdriana M HungIris M HeidMarkus ScholzAlexander TeumerAnna KottgenCristian Pattaro
Published in: Nature genetics (2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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