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dc.contributor.authorErzurumluoglu, A. Mesut
dc.contributor.authorLiu, Mengzhen
dc.contributor.authorJackson, Victoria E.
dc.contributor.authorBarnes, Daniel R.
dc.contributor.authorDatta, Gargi
dc.contributor.authorMelbourne, Carl A.
dc.contributor.authorYoung, Robin
dc.contributor.authorBatini, Chiara
dc.contributor.authorSurendran, Praveen
dc.contributor.authorJiang, Tao
dc.contributor.authorAdnan, Sheikh Daud
dc.contributor.authorAfaq, Saima
dc.contributor.authorAgrawal, Arpana
dc.contributor.authorAltmaier, Elisabeth
dc.contributor.authorAntoniou, Antonis C.
dc.contributor.authorAsselbergs, Folkert W.
dc.contributor.authorBaumbach, Clemens
dc.contributor.authorBierut, Laura
dc.contributor.authorBertelsen, Sarah
dc.contributor.authorBoehnke, Michael
dc.contributor.authorBots, Michiel L.
dc.contributor.authorBrazel, David M
dc.contributor.authorChambers, John C.
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorChen, Chu
dc.contributor.authorCorley, Janie
dc.contributor.authorChou, Yi-Ling
dc.contributor.authorDavid, Sean P.
dc.contributor.authorde Boer, Rudolf A.
dc.contributor.authorde Leeuw, Christiaan A.
dc.contributor.authorDennis, Joe G.
dc.contributor.authorDominiczak, Anna F.
dc.contributor.authorDunning, Alison M.
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorEaton, Charles
dc.contributor.authorElliott, Paul
dc.contributor.authorEvangelou, Evangelos
dc.contributor.authorFaul, Jessica D.
dc.contributor.authorForoud, Tatiana
dc.contributor.authorGoate, Alison
dc.contributor.authorGong, Jian
dc.contributor.authorGrabe, Hans J.
dc.contributor.authorHaessler, Jeff
dc.contributor.authorHaiman, Christopher
dc.contributor.authorHallmans, Göran
dc.contributor.authorHammerschlag, Anke R.
dc.contributor.authorHarris, Sarah E.
dc.contributor.authorHattersley, Andrew
dc.contributor.authorHeath, Andrew
dc.contributor.authorHsu, Chris
dc.contributor.authorIacono, William G.
dc.contributor.authorKanoni, Stavroula
dc.contributor.authorKapoor, Manav
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorKardia, Sharon L.
dc.contributor.authorKarpe, Fredrik
dc.contributor.authorKontto, Jukka
dc.contributor.authorKooner, Jaspal S.
dc.contributor.authorKooperberg, Charles
dc.contributor.authorKuulasmaa, Kari
dc.contributor.authorLaakso, Markku
dc.contributor.authorLai, Dongbing
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorLe, Nhung
dc.contributor.authorLettre, Guillaume
dc.contributor.authorLoukola, Anu
dc.contributor.authorLuan, Jian’an
dc.contributor.authorMadden, Pamela A. F.
dc.contributor.authorMangino, Massimo
dc.contributor.authorMarioni, Riccardo E.
dc.contributor.authorMarouli, Eirini
dc.contributor.authorMarten, Jonathan
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorMcGue, Matt
dc.contributor.authorMichailidou, Kyriaki
dc.contributor.authorMihailov, Evelin
dc.contributor.authorMoayyeri, Alireza
dc.contributor.authorMoitry, Marie
dc.contributor.authorMüller-Nurasyid, Martina
dc.contributor.authorNaheed, Aliya
dc.contributor.authorNauck, Matthias
dc.contributor.authorNeville, Matthew J.
dc.contributor.authorNielsen, Sune Fallgaard
dc.contributor.authorNorth, Kari
dc.contributor.authorPerola, Markus
dc.contributor.authorPharoah, Paul D. P.
dc.contributor.authorPistis, Giorgio
dc.contributor.authorPolderman, Tinca J.
dc.contributor.authorPosthuma, Danielle
dc.contributor.authorPoulter, Neil
dc.contributor.authorQaiser, Beenish
dc.contributor.authorRasheed, Asif
dc.contributor.authorReiner, Alex
dc.contributor.authorRenström, Frida
dc.contributor.authorRice, John
dc.contributor.authorRohde, Rebecca
dc.contributor.authorRolandsson, Olov
dc.contributor.authorSamani, Nilesh J.
dc.contributor.authorSamuel, Maria
dc.contributor.authorSchlessinger, David
dc.contributor.authorScholte, Steven H
dc.contributor.authorScott, Robert A.
dc.contributor.authorSever, Peter
dc.contributor.authorShao, Yaming
dc.contributor.authorShrine, Nick
dc.contributor.authorSmith, Jennifer A.
dc.contributor.authorStarr, John M.
dc.contributor.authorStirrups, Kathleen
dc.contributor.authorStram, Danielle
dc.contributor.authorStringham, Heather M.
dc.contributor.authorTachmazidou, Ioanna
dc.contributor.authorTardif, Jean-Claude
dc.contributor.authorThompson, Deborah J.
dc.contributor.authorTindle, Hilary A.
dc.contributor.authorTragante, Vinicius
dc.contributor.authorTrompet, Stella
dc.contributor.authorTurcot, Valerie
dc.contributor.authorTyrrell, Jessica
dc.contributor.authorVaartjes, Ilonca
dc.contributor.authorvan der Leij, Andries R
dc.contributor.authorvan der Meer, Peter
dc.contributor.authorVarga, Tibor V.
dc.contributor.authorVerweij, Niek
dc.contributor.authorVölzke, Henry
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorWarren, Helen R.
dc.contributor.authorWeir, David R.
dc.contributor.authorWeiss, Stefan
dc.contributor.authorWetherill, Leah
dc.contributor.authorYaghootkar, Hanieh
dc.contributor.authorYavas, Ersin
dc.contributor.authorJiang, Yu
dc.contributor.authorChen, Fang
dc.contributor.authorZhan, Xiaowei
dc.contributor.authorZhang, Weihua
dc.contributor.authorZhao, Wei
dc.contributor.authorZhou, Kaixin
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorBlankenberg, Stefan
dc.contributor.authorCaulfield, Mark J.
dc.contributor.authorChowdhury, Rajiv
dc.contributor.authorCucca, Francesco
dc.contributor.authorDeary, Ian J.
dc.contributor.authorDeloukas, Panos
dc.contributor.authorDi Angelantonio, Emanuele
dc.contributor.authorFerrario, Marco
dc.contributor.authorFerrières, Jean
dc.contributor.authorFranks, Paul W.
dc.contributor.authorFrayling, Tim M.
dc.contributor.authorFrossard, Philippe
dc.contributor.authorHall, Ian P.
dc.contributor.authorHayward, Caroline
dc.contributor.authorJansson, Jan-Håkan
dc.contributor.authorJukema, J. Wouter
dc.contributor.authorKee, Frank
dc.contributor.authorMännistö, Satu
dc.contributor.authorMetspalu, Andres
dc.contributor.authorMunroe, Patricia B.
dc.contributor.authorNordestgaard, Børge Grønne
dc.contributor.authorPalmer, Colin N. A.
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorSattar, Naveed
dc.contributor.authorSpector, Timothy
dc.contributor.authorStrachan, David Peter
dc.contributor.author
dc.contributor.authorvan der Harst, Pim
dc.contributor.authorZeggini, Eleftheria
dc.contributor.authorSaleheen, Danish
dc.contributor.authorButterworth, Adam S.
dc.contributor.authorWain, Louise V.
dc.contributor.authorAbecasis, Goncalo R.
dc.contributor.authorDanesh, John
dc.contributor.authorTobin, Martin D.
dc.contributor.authorVrieze, Scott
dc.contributor.authorLiu, Dajiang J.
dc.contributor.authorHowson, Joanna M. M.
dc.date.accessioned2020-09-25T16:20:27Z
dc.date.available2020-09-25T16:20:27Z
dc.date.issued2019-01-07
dc.date.submitted2018-05-02
dc.identifier.issn1359-4184
dc.identifier.others41380-018-0313-0
dc.identifier.other313
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/310731
dc.description.abstractAbstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10−8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10−8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10−3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/208
dc.subject/692/699/476/5
dc.subject/45/43
dc.subject/45
dc.subjectarticle
dc.titleMeta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
dc.typeArticle
dc.date.updated2020-09-25T16:20:27Z
prism.endingPage2409
prism.issueIdentifier10
prism.publicationNameMolecular Psychiatry
prism.startingPage2392
prism.volume25
dc.identifier.doi10.17863/CAM.57820
dcterms.dateAccepted2018-11-14
rioxxterms.versionofrecord10.1038/s41380-018-0313-0
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidHowson, Joanna M. M. [0000-0001-7618-0050]
dc.identifier.eissn1476-5578
pubs.funder-project-idBritish Heart Foundation (BHF) (SP/09/002, RG/13/13/30194)
pubs.funder-project-idEC | European Research Council (ERC) (268834)


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