6533b82efe1ef96bd1292827
RESEARCH PRODUCT
A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample
Ruth J. F. LoosJing Hua ZhaoNicole SoranzoNicole SoranzoPanos DeloukasOzren PolasekMassimo ManginoRaquel GranellWilmar IglEva AlbrechtNoor KalshekerDavid HadleyDavid HadleyCaroline HaywardVeronique VitartTaina RantanenJennie HuiJennie HuiJennifer E. HuffmanEmmanouela RepapiEmmanouela RepapiGemma CadbyGemma CadbyAlicja R. RudnickaIan P. HallSven GläserIgor RudanIgor RudanAnna-liisa HartikainenLinda MustelinLyle J. PalmerLyle J. PalmerUlf GyllenstenWendy L. McardleIda SurakkaIda SurakkaMedea ImbodenPaul BurtonJames F. WilsonIvica GrkovićBeate KochAdaikalavan RamasamyAdaikalavan RamasamyJoachim HeinrichÅSa JohanssonAnneli PoutaMaría Soler ArtigasNicole Probst-henschNicole Probst-henschArthur W. MuskArthur W. MuskGeorg HomuthStipan JankovićJohn HendersonInês BarrosoInês BarrosoLouise V. WainNick ShrinePaul ElliottSarah H. WildToby JohnsonHenry VölzkeMarjo-riitta JärvelinNicholas J. WarehamDavid M. EvansLina ZgagaHarry CampbellGhazal ZaboliIan SayersDavid P. StrachanMartin D. TobinAlan F. WrightJaakko KaprioJaakko KaprioTim D. SpectorGuangju ZhaiMa'en Obeidatsubject
PulmonologyChronic Obstructive Pulmonary DiseasesEpidemiologyVital Capacitylcsh:MedicineGenome-wide association studyBioinformaticsPDE4DPulmonary function testingPulmonary Disease Chronic Obstructive0302 clinical medicineForced Expiratory VolumePHOSPHODIESTERASE 4D GENElcsh:ScienceLungRISK0303 health scienceseducation.field_of_studyCOPDMultidisciplinaryAlpha 1-antitrypsin deficiencyGreat BritainALPHA(1)-ANTITRYPSIN DEFICIENCYta3141ta3142respiratory system3142 Public health care science environmental and occupational health3. Good healthRespiratory Function Testsmedicine.anatomical_structureGenetic EpidemiologyScience & Technology - Other TopicsMedicineBiological MarkersHEALTHResearch Articlemedicine.medical_specialtyGeneral Science & TechnologyPopulationObstructive pulmonary-disease; Phosphodiesterase 4D gene; Alpha(1)-antitrypsin deficiency; Health; PDE4D; RiskPolymorphism Single NucleotideOBSTRUCTIVE PULMONARY-DISEASE03 medical and health sciencesMeta-Analysis as TopicMolecular geneticsMD MultidisciplinarymedicineGeneticsGenome-Wide Association StudiesHumansGenetic Predisposition to DiseaseeducationBiology030304 developmental biologyAsthmaScience & TechnologyLungMULTIDISCIPLINARY SCIENCESbusiness.industryGenome Humanlcsh:RSmoking Related DisordersSpiroMeta Consortiummedicine.diseaseUnited KingdomAsthmarespiratory tract diseasesGenetics of Diseaselcsh:Qbusiness030217 neurology & neurosurgeryBiomarkersGenome-Wide Association Studydescription
Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). OBJECTIVES: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. METHODS: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-4)) among ever-smokers.CONCLUSIONS: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV(1) among smokers in the general population.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-05-20 |