TY - JOUR
T1 - Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.
JF - Molecular Psychiatry
Y1 - 2020
A1 - Erzurumluoglu, A Mesut
A1 - Liu, Mengzhen
A1 - Jackson, Victoria E
A1 - Barnes, Daniel R
A1 - Datta, Gargi
A1 - Melbourne, Carl A
A1 - Young, Robin
A1 - Batini, Chiara
A1 - Surendran, Praveen
A1 - Jiang, Tao
A1 - Adnan, Sheikh Daud
A1 - Afaq, Saima
A1 - Agrawal, Arpana
A1 - Altmaier, Elisabeth
A1 - Antoniou, Antonis C
A1 - Asselbergs, Folkert W
A1 - Baumbach, Clemens
A1 - Laura Bierut
A1 - Bertelsen, Sarah
A1 - Boehnke, Michael
A1 - Bots, Michiel L
A1 - Brazel, David M
A1 - Chambers, John C
A1 - Chang-Claude, Jenny
A1 - Chen, Chu
A1 - Corley, Janie
A1 - Chou, Yi-Ling
A1 - David, Sean P
A1 - de Boer, Rudolf A
A1 - Christiaan de Leeuw
A1 - Joe G Dennis
A1 - Dominiczak, Anna F
A1 - Dunning, Alison M
A1 - Easton, Douglas F
A1 - Charles B Eaton
A1 - Elliott, Paul
A1 - Evangelou, Evangelos
A1 - Jessica Faul
A1 - Tatiana Foroud
A1 - Goate, Alison
A1 - Gong, Jian
A1 - Hans-Jörgen Grabe
A1 - Jeffrey Haessler
A1 - Christopher A Haiman
A1 - Hallmans, Göran
A1 - Anke R Hammerschlag
A1 - Sarah E Harris
A1 - Andrew T Hattersley
A1 - Andrew C Heath
A1 - Hsu, Chris
A1 - Iacono, William G
A1 - Kanoni, Stavroula
A1 - Kapoor, Manav
A1 - Kaprio, Jaakko
A1 - Sharon L R Kardia
A1 - Karpe, Fredrik
A1 - Kontto, Jukka
A1 - Kooner, Jaspal S
A1 - Charles Kooperberg
A1 - Kuulasmaa, Kari
A1 - Laakso, Markku
A1 - Lai, Dongbing
A1 - Langenberg, Claudia
A1 - Le, Nhung
A1 - Lettre, Guillaume
A1 - Loukola, Anu
A1 - Luan, Jian'an
A1 - Pamela A F Madden
A1 - Mangino, Massimo
A1 - Riccardo E Marioni
A1 - Marouli, Eirini
A1 - Marten, Jonathan
A1 - Nicholas G Martin
A1 - McGue, Matt
A1 - Michailidou, Kyriaki
A1 - Mihailov, Evelin
A1 - Moayyeri, Alireza
A1 - Moitry, Marie
A1 - Müller-Nurasyid, Martina
A1 - Naheed, Aliya
A1 - Nauck, Matthias
A1 - Neville, Matthew J
A1 - Sune Fallgaard Nielsen
A1 - Kari E North
A1 - Markus Perola
A1 - Pharoah, Paul D P
A1 - Pistis, Giorgio
A1 - Tinca J Polderman
A1 - Posthuma, Danielle
A1 - Neil Poulter
A1 - Qaiser, Beenish
A1 - Rasheed, Asif
A1 - Reiner, Alex
A1 - Renstrom, Frida
A1 - Rice, John
A1 - Rohde, Rebecca
A1 - Rolandsson, Olov
A1 - Nilesh J Samani
A1 - Samuel, Maria
A1 - Schlessinger, David
A1 - H Steven Scholte
A1 - Scott, Robert A
A1 - Peter Sever
A1 - Shao, Yaming
A1 - Shrine, Nick
A1 - Smith, Jennifer A
A1 - John M Starr
A1 - Kathleen E Stirrups
A1 - Stram, Danielle
A1 - Heather M Stringham
A1 - Tachmazidou, Ioanna
A1 - Tardif, Jean-Claude
A1 - Thompson, Deborah J
A1 - Hilary A Tindle
A1 - Tragante, Vinicius
A1 - Trompet, Stella
A1 - Turcot, Valérie
A1 - Tyrrell, Jessica
A1 - Vaartjes, Ilonca
A1 - Van Der Leij, Andries R
A1 - van der Meer, Peter
A1 - Varga, Tibor V
A1 - Verweij, Niek
A1 - Völzke, Henry
A1 - Wareham, Nicholas J
A1 - Warren, Helen R
A1 - David R Weir
A1 - Weiss, Stefan
A1 - Wetherill, Leah
A1 - Yaghootkar, Hanieh
A1 - Yavas, Ersin
A1 - Jiang, Yu
A1 - Chen, Fang
A1 - Zhan, Xiaowei
A1 - Zhang, Weihua
A1 - Zhao, Wei
A1 - Zhao, Wei
A1 - Zhou, Kaixin
A1 - Amouyel, Philippe
A1 - Blankenberg, Stefan
A1 - Caulfield, Mark J
A1 - Chowdhury, Rajiv
A1 - Francesco Cucca
A1 - Ian J Deary
A1 - Deloukas, Panos
A1 - Di Angelantonio, Emanuele
A1 - Marco M Ferrario
A1 - Ferrières, Jean
A1 - Franks, Paul W
A1 - Timothy M Frayling
A1 - Frossard, Philippe
A1 - Hall, Ian P
A1 - Caroline Hayward
A1 - Jansson, Jan-Håkan
A1 - Jukema, J Wouter
A1 - Kee, Frank
A1 - Männistö, Satu
A1 - Andres Metspalu
A1 - Munroe, Patricia B
A1 - Børge G Nordestgaard
A1 - Palmer, Colin N A
A1 - Veikko Salomaa
A1 - Sattar, Naveed
A1 - Timothy Spector
A1 - David P Strachan
A1 - van der Harst, Pim
A1 - Zeggini, Eleftheria
A1 - Saleheen, Danish
A1 - Adam S Butterworth
A1 - Wain, Louise V
A1 - Gonçalo R Abecasis
A1 - Danesh, John
A1 - Tobin, Martin D
A1 - Scott Vrieze
A1 - Liu, Dajiang J
A1 - Howson, Joanna M M
KW - Biological Specimen Banks
KW - Databases, Factual
KW - Europe
KW - Exome
KW - Female
KW - Genetic Loci
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Smoking
KW - United Kingdom
AB - 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 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) 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) 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.

VL - 25
IS - 10
ER -