Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. / 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 C; 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; Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ consortium.
In: MOL PSYCHIATR, Vol. 25, No. 10, 10.2020, p. 2392-2409.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
AU - Erzurumluoglu, A Mesut
AU - Liu, Mengzhen
AU - Jackson, Victoria E
AU - Barnes, Daniel R
AU - Datta, Gargi
AU - Melbourne, Carl A
AU - Young, Robin
AU - Batini, Chiara
AU - Surendran, Praveen
AU - Jiang, Tao
AU - Adnan, Sheikh Daud
AU - Afaq, Saima
AU - Agrawal, Arpana
AU - Altmaier, Elisabeth
AU - Antoniou, Antonis C
AU - Asselbergs, Folkert W
AU - Baumbach, Clemens
AU - Bierut, Laura
AU - Bertelsen, Sarah
AU - Boehnke, Michael
AU - Bots, Michiel L
AU - Brazel, David M
AU - Chambers, John C
AU - Chang-Claude, Jenny
AU - Chen, Chu
AU - Corley, Janie
AU - Chou, Yi-Ling
AU - David, Sean P
AU - de Boer, Rudolf A
AU - de Leeuw, Christiaan A
AU - Dennis, Joe G
AU - Dominiczak, Anna F
AU - Dunning, Alison M
AU - Easton, Douglas F
AU - Eaton, Charles
AU - Elliott, Paul
AU - Evangelou, Evangelos
AU - Faul, Jessica D
AU - Foroud, Tatiana
AU - Goate, Alison
AU - Gong, Jian
AU - Grabe, Hans J
AU - Haessler, Jeff
AU - Haiman, Christopher
AU - Hallmans, Göran
AU - Hammerschlag, Anke R
AU - Harris, Sarah E
AU - Hattersley, Andrew
AU - Heath, Andrew
AU - Hsu, Chris
AU - Iacono, William G
AU - Kanoni, Stavroula
AU - Kapoor, Manav
AU - Kaprio, Jaakko
AU - Kardia, Sharon L
AU - Karpe, Fredrik
AU - Kontto, Jukka
AU - Kooner, Jaspal S
AU - Kooperberg, Charles
AU - Kuulasmaa, Kari
AU - Laakso, Markku
AU - Lai, Dongbing
AU - Langenberg, Claudia
AU - Le, Nhung
AU - Lettre, Guillaume
AU - Loukola, Anu
AU - Luan, Jian'an
AU - Madden, Pamela A F
AU - Mangino, Massimo
AU - Marioni, Riccardo E
AU - Marouli, Eirini
AU - Marten, Jonathan
AU - Martin, Nicholas G
AU - McGue, Matt
AU - Michailidou, Kyriaki
AU - Mihailov, Evelin
AU - Moayyeri, Alireza
AU - Moitry, Marie
AU - Müller-Nurasyid, Martina
AU - Naheed, Aliya
AU - Nauck, Matthias
AU - Neville, Matthew J
AU - Nielsen, Sune Fallgaard
AU - North, Kari
AU - Perola, Markus
AU - Pharoah, Paul D P
AU - Pistis, Giorgio
AU - Polderman, Tinca J
AU - Posthuma, Danielle
AU - Poulter, Neil
AU - Qaiser, Beenish
AU - Rasheed, Asif
AU - Reiner, Alex
AU - Renström, Frida
AU - Rice, John
AU - Rohde, Rebecca
AU - Rolandsson, Olov
AU - Samani, Nilesh J
AU - Samuel, Maria
AU - Schlessinger, David
AU - Scholte, Steven H
AU - Scott, Robert A
AU - Sever, Peter
AU - Shao, Yaming
AU - Shrine, Nick
AU - Smith, Jennifer A
AU - Starr, John M
AU - Stirrups, Kathleen
AU - Stram, Danielle
AU - Stringham, Heather M
AU - Tachmazidou, Ioanna
AU - Tardif, Jean-Claude
AU - Thompson, Deborah J
AU - Tindle, Hilary A
AU - Tragante, Vinicius
AU - Trompet, Stella
AU - Turcot, Valerie
AU - Tyrrell, Jessica
AU - Vaartjes, Ilonca
AU - van der Leij, Andries R
AU - van der Meer, Peter
AU - Varga, Tibor V
AU - Verweij, Niek
AU - Völzke, Henry
AU - Wareham, Nicholas J
AU - Warren, Helen R
AU - Weir, David R
AU - Weiss, Stefan
AU - Wetherill, Leah
AU - Yaghootkar, Hanieh
AU - Yavas, Ersin
AU - Jiang, Yu
AU - Chen, Fang
AU - Zhan, Xiaowei
AU - Zhang, Weihua
AU - Zhao, Wei
AU - Zhao, Wei
AU - Zhou, Kaixin
AU - Amouyel, Philippe
AU - Blankenberg, Stefan
AU - Caulfield, Mark J
AU - Chowdhury, Rajiv
AU - Cucca, Francesco
AU - Deary, Ian J
AU - Deloukas, Panos
AU - Di Angelantonio, Emanuele
AU - Ferrario, Marco
AU - Ferrières, Jean
AU - Franks, Paul W
AU - Frayling, Tim M
AU - Frossard, Philippe
AU - Hall, Ian P
AU - Hayward, Caroline
AU - Jansson, Jan-Håkan
AU - Jukema, J Wouter
AU - Kee, Frank
AU - Männistö, Satu
AU - Metspalu, Andres
AU - Munroe, Patricia B
AU - Nordestgaard, Børge Grønne
AU - Palmer, Colin N A
AU - Salomaa, Veikko
AU - Sattar, Naveed
AU - Spector, Timothy
AU - Strachan, David Peter
AU - van der Harst, Pim
AU - Zeggini, Eleftheria
AU - Saleheen, Danish
AU - Butterworth, Adam S
AU - Wain, Louise V
AU - Abecasis, Goncalo R
AU - Danesh, John
AU - Tobin, Martin D
AU - Vrieze, Scott
AU - Liu, Dajiang J
AU - Howson, Joanna M M
AU - Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ consortium
PY - 2020/10
Y1 - 2020/10
N2 - 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.
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 × 10-8 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.
U2 - 10.1038/s41380-018-0313-0
DO - 10.1038/s41380-018-0313-0
M3 - SCORING: Journal article
C2 - 30617275
VL - 25
SP - 2392
EP - 2409
JO - MOL PSYCHIATR
JF - MOL PSYCHIATR
SN - 1359-4184
IS - 10
ER -
