6533b7d0fe1ef96bd125b8c4

RESEARCH PRODUCT

Genome-wide association study identifies five loci associated with lung function

H GrallertFredrik NybergFredrik NybergSarah H. WildInês BarrosoJohn W. HollowayVeronique VitartKjell TorénRichard W MorrisNicole Probst-henschNicole Probst-henschTaina RantanenS.g. WannametheeOlin A-c.Jennie HuiJennie HuiMedea ImbodenPaul ElliottPaul ElliottNicole SoranzoNicole SoranzoOzren PolasekSven GläserNabila Bouatia-najiWendy L. McardleAndrew K. MacleodWilmar IglEmmanouela RepapiAroon D. HingoraniPhilippe FroguelPhilippe FroguelNicholas J. WarehamÅSa JohanssonHarry CampbellÅSa Torinsson NaluaiShah EbrahimTricia M. MckeeverIgor RudanIgor RudanMika KähönenJohn BrittonLinda MustelinLoos Rjf.Adaikalavan RamasamyIvica GrkovićBeate KochJing Hua ZhaoMark E. CooperJarvelin M-r.Peter H. WhincupGeorge Davey SmithMa'en ObeidatJennifer E. HuffmanE AlbrechtElaine M. DennisonMarkku HeliövaaraH E WichmannAlan F. WrightLeena PeltonenLeena PeltonenLeena PeltonenE SchnabelIan D. PavordGeorg HomuthPaul BurtonCyrus CooperCyrus CooperIda SurakkaIda SurakkaRaquel GranellHolger SchulzJaakko KaprioJaakko KaprioJohn HendersonJérôme DelplanqueCaroline HaywardStipan JankovićStefan KarraschDebbie A LawlorToby JohnsonSamuli RipattiSamuli RipattiAlan JamesLyle J. PalmerLyle J. PalmerUlf GyllenstenAndrew D. MorrisPanagiotis DeloukasAnneli PoutaDavid M. EvansLina ZgagaHenry VölzkeAlicja R. RudnickaHartikainen A-l.Hartikainen A-l.Hartikainen A-l.Seif O. ShaheenTim D. SpectorGuangju ZhaiCatherine JacksonMassimo ManginoIan P. HallIan SayersDavid P. StrachanMartin D. TobinDavid J. PorteousLouise V. WainJohn D BlakeyJames F. WilsonGhazal Zaboli

subject

OncologySpirometryMalemedicine.medical_specialtyVital capacityPopulationReceptor for Advanced Glycation End ProductsVital CapacityGenome-wide association studyBiologyPolymorphism Single NucleotideArticlePulmonary function testing03 medical and health sciencesFEV1/FVC ratioPulmonary Disease Chronic Obstructive0302 clinical medicineMeta-Analysis as TopicInternal medicineTensinsForced Expiratory VolumeGeneticsmedicineHumansRNA MessengerReceptors ImmunologiceducationLung030304 developmental biologyGlutathione Transferase0303 health scienceseducation.field_of_studyCOPDmedicine.diagnostic_testGenome HumanGene Expression ProfilingMicrofilament Proteinsrespiratory systemmedicine.disease3. Good healthRespiratory Function Tests030228 respiratory systemSpirometryImmunologyFemaleReceptors Serotonin 5-HT4Hedgehog interacting proteinThrombospondinsGenome-Wide Association Study

description

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

yearjournalcountryeditionlanguage
2009-12-13
10.1038/ng.501https://europepmc.org/articles/PMC2862965/