@article {12124,
	title = {Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.},
	journal = {Molecular Psychiatry},
	volume = {25},
	year = {2020},
	pages = {2392-2409},
	abstract = {<p>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 {\texttimes} 10 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 {\texttimes} 10) 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 {\texttimes} 10) 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.</p>},
	keywords = {Biological Specimen Banks, Databases, Factual, Europe, Exome, Female, Genetic Loci, Humans, Male, Polymorphism, Single Nucleotide, Smoking, United Kingdom},
	issn = {1476-5578},
	doi = {10.1038/s41380-018-0313-0},
	author = {Erzurumluoglu, A Mesut and Liu, Mengzhen and Jackson, Victoria E and Barnes, Daniel R and Datta, Gargi and Melbourne, Carl A and Young, Robin and Batini, Chiara and Surendran, Praveen and Jiang, Tao and Adnan, Sheikh Daud and Afaq, Saima and Agrawal, Arpana and Altmaier, Elisabeth and Antoniou, Antonis C and Asselbergs, Folkert W and Baumbach, Clemens and Laura Bierut and Bertelsen, Sarah and Boehnke, Michael and Bots, Michiel L and Brazel, David M and Chambers, John C and Chang-Claude, Jenny and Chen, Chu and Corley, Janie and Chou, Yi-Ling and David, Sean P and de Boer, Rudolf A and Christiaan de Leeuw and Joe G Dennis and Dominiczak, Anna F and Dunning, Alison M and Easton, Douglas F and Charles B Eaton and Elliott, Paul and Evangelou, Evangelos and Jessica Faul and Tatiana Foroud and Goate, Alison and Gong, Jian and Hans-J{\"o}rgen Grabe and Jeffrey Haessler and Christopher A Haiman and Hallmans, G{\"o}ran and Anke R Hammerschlag and Sarah E Harris and Andrew T Hattersley and Andrew C Heath and Hsu, Chris and Iacono, William G and Kanoni, Stavroula and Kapoor, Manav and Kaprio, Jaakko and Sharon L R Kardia and Karpe, Fredrik and Kontto, Jukka and Kooner, Jaspal S and Charles Kooperberg and Kuulasmaa, Kari and Laakso, Markku and Lai, Dongbing and Langenberg, Claudia and Le, Nhung and Lettre, Guillaume and Loukola, Anu and Luan, Jian{\textquoteright}an and Pamela A F Madden and Mangino, Massimo and Riccardo E Marioni and Marouli, Eirini and Marten, Jonathan and Nicholas G Martin and McGue, Matt and Michailidou, Kyriaki and Mihailov, Evelin and Moayyeri, Alireza and Moitry, Marie and M{\"u}ller-Nurasyid, Martina and Naheed, Aliya and Nauck, Matthias and Neville, Matthew J and Sune Fallgaard Nielsen and Kari E North and Markus Perola and Pharoah, Paul D P and Pistis, Giorgio and Tinca J Polderman and Posthuma, Danielle and Neil Poulter and Qaiser, Beenish and Rasheed, Asif and Reiner, Alex and Renstrom, Frida and Rice, John and Rohde, Rebecca and Rolandsson, Olov and Nilesh J Samani and Samuel, Maria and Schlessinger, David and H Steven Scholte and Scott, Robert A and Peter Sever and Shao, Yaming and Shrine, Nick and Smith, Jennifer A and John M Starr and Kathleen E Stirrups and Stram, Danielle and Heather M Stringham and Tachmazidou, Ioanna and Tardif, Jean-Claude and Thompson, Deborah J and Hilary A Tindle and Tragante, Vinicius and Trompet, Stella and Turcot, Val{\'e}rie and Tyrrell, Jessica and Vaartjes, Ilonca and Van Der Leij, Andries R and van der Meer, Peter and Varga, Tibor V and Verweij, Niek and V{\"o}lzke, Henry and Wareham, Nicholas J and Warren, Helen R and David R Weir and Weiss, Stefan and Wetherill, Leah and Yaghootkar, Hanieh and Yavas, Ersin and Jiang, Yu and Chen, Fang and Zhan, Xiaowei and Zhang, Weihua and Zhao, Wei and Zhao, Wei and Zhou, Kaixin and Amouyel, Philippe and Blankenberg, Stefan and Caulfield, Mark J and Chowdhury, Rajiv and Francesco Cucca and Ian J Deary and Deloukas, Panos and Di Angelantonio, Emanuele and Marco M Ferrario and Ferri{\`e}res, Jean and Franks, Paul W and Timothy M Frayling and Frossard, Philippe and Hall, Ian P and Caroline Hayward and Jansson, Jan-H{\r a}kan and Jukema, J Wouter and Kee, Frank and M{\"a}nnist{\"o}, Satu and Andres Metspalu and Munroe, Patricia B and B{\o}rge G Nordestgaard and Palmer, Colin N A and Veikko Salomaa and Sattar, Naveed and Timothy Spector and David P Strachan and van der Harst, Pim and Zeggini, Eleftheria and Saleheen, Danish and Adam S Butterworth and Wain, Louise V and Gon{\c c}alo R Abecasis and Danesh, John and Tobin, Martin D and Scott Vrieze and Liu, Dajiang J and Howson, Joanna M M}
}
