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Title: | Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci | Authors: | Erzurumluoglu, A Mesut Liu, Mengzhen Jackson, Victoria E Barnes, Daniel R Datta, Gargi Melbourne, Carl A Young, Robin Batini, Chiara Surendran, Praveen Jiang, Tao Adnan, Sheikh Daud Afaq, Saima Agrawal, Arpana Altmaier, Elisabeth Antoniou, Antonis C Asselbergs, Folkert W Baumbach, Clemens Bierut, Laura Bertelsen, Sarah Boehnke, Michael Bots, Michiel L Brazel, David M Chambers, John Campbell Chang-Claude, Jenny Chen, Chu Corley, Janie Chou, Yi-Ling David, Sean P de Boer, Rudolf A de Leeuw, Christiaan A Dennis, Joe G Dominiczak, Anna F Dunning, Alison M Easton, Douglas F Eaton, Charles Elliott, Paul Evangelou, Evangelos Faul, Jessica D Foroud, Tatiana Goate, Alison Gong, Jian Grabe, Hans J Haessler, Jeff Haiman, Christopher Hallmans, Göran Hammerschlag, Anke R Harris, Sarah E Hattersley, Andrew Heath, Andrew Hsu, Chris Iacono, William G Kanoni, Stavroula Kapoor, Manav Kaprio, Jaakko Kardia, Sharon L Karpe, Fredrik Kontto, Jukka Kooner, Jaspal S Kooperberg, Charles Kuulasmaa, Kari Laakso, Markku Lai, Dongbing Langenberg, Claudia Le, Nhung Lettre, Guillaume Loukola, Anu Luan, Jian'an Madden, Pamela A F Mangino, Massimo Marioni, Riccardo E Marouli, Eirini Marten, Jonathan Martin, Nicholas G McGue, Matt Michailidou, Kyriaki Mihailov, Evelin Moayyeri, Alireza Moitry, Marie Müller-Nurasyid, Martina Naheed, Aliya Nauck, Matthias Neville, Matthew J Nielsen, Sune Fallgaard North, Kari Perola, Markus Pharoah, Paul D P Pistis, Giorgio Polderman, Tinca J Posthuma, Danielle Poulter, Neil Qaiser, Beenish Rasheed, Asif Reiner, Alex Renström, Frida Rice, John Rohde, Rebecca Rolandsson, Olov Samani, Nilesh J Samuel, Maria Schlessinger, David Scholte, Steven H Scott, Robert A Sever, Peter Shao, Yaming Shrine, Nick Smith, Jennifer A Starr, John M Stirrups, Kathleen Stram, Danielle Stringham, Heather M Tachmazidou, Ioanna Tardif, Jean-Claude Thompson, Deborah J Tindle, Hilary A Tragante, Vinicius Trompet, Stella Turcot, Valerie Tyrrell, Jessica Vaartjes, Ilonca van der Leij, Andries R van der Meer, Peter Varga, Tibor V Verweij, Niek Völzke, Henry Wareham, Nicholas J Warren, Helen R Weir, David R Weiss, Stefan Wetherill, Leah Yaghootkar, Hanieh Yavas, Ersin Jiang, Yu Chen, Fang Zhan, Xiaowei Zhang, Weihua Zhao, Wei Zhao, Wei Zhou, Kaixin Amouyel, Philippe Blankenberg, Stefan Caulfield, Mark J Chowdhury, Rajiv Cucca, Francesco Deary, Ian J Deloukas, Panos Di Angelantonio, Emanuele Ferrario, Marco Ferrières, Jean Franks, Paul W Frayling, Tim M Frossard, Philippe Hall, Ian P Hayward, Caroline Jansson, Jan-Håkan Jukema, J Wouter Kee, Frank Männistö, Satu Metspalu, Andres Munroe, Patricia B Nordestgaard, Børge Grønne Palmer, Colin N A Salomaa, Veikko Sattar, Naveed Spector, Timothy Strachan, David Peter van der Harst, Pim Zeggini, Eleftheria Saleheen, Danish Butterworth, Adam S Wain, Louise V Abecasis, Goncalo R Danesh, John Tobin, Martin D Vrieze, Scott Liu, Dajiang J Howson, Joanna M M |
Keywords: | Science::Medicine | Issue Date: | 2020 | Source: | Erzurumluoglu, A. M., Liu, M., Jackson, V. E., Barnes, D. R., Datta, G., Melbourne, C. A., Young, R., Batini, C., Surendran, P., Jiang, T., Adnan, S. D., Afaq, S., Agrawal, A., Altmaier, E., Antoniou, A. C., Asselbergs, F. W., Baumbach, C., Bierut, L., Bertelsen, S., ...Howson, J. M. M. (2020). Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. Molecular Psychiatry, 25(10), 2392-2409. https://dx.doi.org/10.1038/s41380-018-0313-0 | Journal: | Molecular Psychiatry | Abstract: | 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. | URI: | https://hdl.handle.net/10356/146952 | ISSN: | 1359-4184 | DOI: | 10.1038/s41380-018-0313-0 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Rights: | © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
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