Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.
Florence DemenaisPatricia Margaritte-JeanninKathleen C BarnesWilliam O C M CooksonJanine AltmüllerWei AngR Graham BarrTerri H BeatyAllan B BeckerJohn P BeilbyHans BisgaardUnnur Steina BjornsdottirEugene BleeckerKlaus BønnelykkeDorret I BoomsmaEmmanuelle BouzigonChristopher E BrightlingMyriam BrossardGuy G BrusselleEsteban BurchardKristin M BurkartAndrew BushMoira Chan-YeungKian Fan ChungAlexessander Couto AlvesJohn A CurtinAdnan CustovicDenise DaleyJohan C de JongsteBlanca E Del-Rio-NavarroKathleen M DonohueLiesbeth DuijtsCeleste EngJohan G ErikssonMartin FarrallYuliya FedorovaBjarke FeenstraManuel A R Ferreiranull nullMaxim B FreidinZofia GajdosJim GaudermanUlrike GehringFrank GellerJon GenuneitSina A GharibFrank GillilandRaquel GranellPenelope E GravesDaníel F GuðbjartssonTari HaahtelaSusan R HeckbertDick HeederikJoachim HeinrichMarkku HeliövaaraJohn HendersonBlanca E HimesHiroshi HiroseJoel N HirschhornAlbert HofmanPatrick HoltJouke HottengaThomas J HudsonJennie HuiMedea ImbodenVladimir IvanovVincent W V JaddoeAlan JamesChrister JansonMarjo-Riitta JarvelinDeborah JarvisGraham JonesIngileif JónsdóttirPekka JousilahtiMichael KabeschMika KähönenDavid B KantorAlexandra S KarunasElza K KhusnutdinovaGerard H KoppelmanAnita L KozyrskyjEskil KreinerMichiaki KuboRajesh KumarAshish KumarMikko KuokkanenLies LahousseTarja LaitinenCatherine LapriseMark LathropSusanne LauYoung-Ae LeeTerho LehtimäkiSébastien LetortAlbert M LevinGuo LiLiming LiangLaura R LoehrStephanie J LondonDaan W LothAni ManichaikulIngo MarenholzFernando J MartinezMelanie C MathesonRasika A MathiasKenji MatsumotoHamdi MbarekWendy L McArdleMads MelbyeErik MelénDeborah MeyersSven MichelHamida MohamdiArthur W MuskRachel A MyersMaartje A E NieuwenhuisEmiko NoguchiGeorge T O'ConnorLudmila M OgorodovaCameron D PalmerAarno PalotieJulie E ParkCraig E PennellGöran PershagenAlexey PolonikovDirkje S PostmaNicole Probst-HenschValery P PuzyrevBenjamin A RabyOlli T RaitakariAdaikalavan RamasamyStephen S RichColin F RobertsonIsabelle RomieuMuhammad T SalamVeikko SalomaaVivi SchlünssenRobert ScottPolina A SelivanovaTorben SigsgaardAngela SimpsonValérie SirouxLewis J SmithMaria SolodilovaMarie StandlKari StefanssonDavid P StrachanBruno H StrickerAtsushi TakahashiPhilip J ThompsonGudmar ThorleifssonUnnur ThorsteinsdottirCarla M T TieslerDara G TorgersonTatsuhiko TsunodaAndré G UitterlindenRalf J P van der ValkAmaury VaysseSailaja VedantamAndrea von BergErika Von MutiusJudith M VonkJohannes WaageNick J WarehamScott T WeissWendy B WhiteMagnus WickmanElisabeth WidénGonneke WillemsenL Keoki WilliamsInge M WoutersJames J YangJing Hua ZhaoMiriam F MoffattCarole OberDan L NicolaePublished in: Nature genetics (2017)
We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.