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dc.contributor.authorDijkstra, Akkelies E.en_US
dc.contributor.authorSmolonska, Joannaen_US
dc.contributor.authorvan den Berge, Maartenen_US
dc.contributor.authorWijmenga, Ciskaen_US
dc.contributor.authorZanen, Pieteren_US
dc.contributor.authorLuinge, Marjan A.en_US
dc.contributor.authorPlatteel, Mathieuen_US
dc.contributor.authorLammers, Jan-Willemen_US
dc.contributor.authorDahlback, Magnusen_US
dc.contributor.authorTosh, Kerrieen_US
dc.contributor.authorHiemstra, Pieter S.en_US
dc.contributor.authorSterk, Peter J.en_US
dc.contributor.authorSpira, Avien_US
dc.contributor.authorVestbo, Jorgenen_US
dc.contributor.authorNordestgaard, Borge G.en_US
dc.contributor.authorBenn, Marianneen_US
dc.contributor.authorNielsen, Sune F.en_US
dc.contributor.authorDahl, Mortenen_US
dc.contributor.authorVerschuren, W. Moniqueen_US
dc.contributor.authorPicavet, H. Susan J.en_US
dc.contributor.authorSmit, Henriette A.en_US
dc.contributor.authorOwsijewitsch, Michaelen_US
dc.contributor.authorKauczor, Hans U.en_US
dc.contributor.authorde Koning, Harry J.en_US
dc.contributor.authorNizankowska-Mogilnicka, Evaen_US
dc.contributor.authorMejza, Filipen_US
dc.contributor.authorNastalek, Pawelen_US
dc.contributor.authorvan Diemen, Cleo C.en_US
dc.contributor.authorCho, Michael H.en_US
dc.contributor.authorSilverman, Edwin K.en_US
dc.contributor.authorCrapo, James D.en_US
dc.contributor.authorBeaty, Terri H.en_US
dc.contributor.authorLomas, David A.en_US
dc.contributor.authorBakke, Peren_US
dc.contributor.authorGulsvik, Amunden_US
dc.contributor.authorBossé, Yohanen_US
dc.contributor.authorObeidat, M. A.en_US
dc.contributor.authorLoth, Daan W.en_US
dc.contributor.authorLahousse, Liesen_US
dc.contributor.authorRivadeneira, Fernandoen_US
dc.contributor.authorUitterlinden, Andre G.en_US
dc.contributor.authorHofman, Andreen_US
dc.contributor.authorStricker, Bruno H.en_US
dc.contributor.authorBrusselle, Guy G.en_US
dc.contributor.authorvan Duijn, Cornelia M.en_US
dc.contributor.authorBrouwer, Uilkeen_US
dc.contributor.authorKoppelman, Gerard H.en_US
dc.contributor.authorVonk, Judith M.en_US
dc.contributor.authorNawijn, Martijn C.en_US
dc.contributor.authorGroen, Harry J. M.en_US
dc.contributor.authorTimens, Wimen_US
dc.contributor.authorBoezen, H. Marikeen_US
dc.contributor.authorPostma, Dirkje S.en_US
dc.date.accessioned2014-05-06T16:17:36Z
dc.date.issued2014en_US
dc.identifier.citationDijkstra, A. E., J. Smolonska, M. van den Berge, C. Wijmenga, P. Zanen, M. A. Luinge, M. Platteel, et al. 2014. “Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study.” PLoS ONE 9 (4): e91621. doi:10.1371/journal.pone.0091621. http://dx.doi.org/10.1371/journal.pone.0091621.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12152914
dc.description.abstractBackground: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10−6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10−9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0091621en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979657/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectComputational Biologyen
dc.subjectGenome Analysisen
dc.subjectTranscriptome Analysisen
dc.subjectGenome Expression Analysisen
dc.subjectGenome-Wide Association Studiesen
dc.subjectGeneticsen
dc.subjectGenomicsen
dc.subjectFunctional Genomicsen
dc.subjectPsychologyen
dc.subjectAddictionen
dc.subjectDrug Addictionen
dc.subjectRecreational Drug Addictionen
dc.subjectMedicine and Health Sciencesen
dc.subjectEpidemiologyen
dc.subjectClinical Epidemiologyen
dc.subjectEnvironmental Epidemiologyen
dc.subjectEpidemiological Methods and Statisticsen
dc.subjectGenetic Epidemiologyen
dc.subjectLifecourse Epidemiologyen
dc.subjectPulmonologyen
dc.subjectChronic Obstructive Pulmonary Diseaseen
dc.subjectEnvironmental and Occupational Lung Diseasesen
dc.subjectRespiratory Infectionsen
dc.titleSusceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Studyen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorCho, Michael H.en_US
dc.date.available2014-05-06T16:17:36Z
dc.identifier.doi10.1371/journal.pone.0091621*
dash.authorsorderedfalse
dash.contributor.affiliatedCho, Michael
dash.contributor.affiliatedSilverman, Edwin


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