Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146952
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
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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