Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Amy R. Bentley (1) , Yun J. Sung (2) , Michael R. Brown (3) , Thomas W. Winkler (4) , Aldi T. Kraja (2) , Ioanna Ntalla (5) , Karen Schwander (2) , Daniel I. Chasman (6, 7) , Elise Lim (8) , Xuan Deng (8) , Xiuqing Guo (9) , Jingmin Liu (10) , Yingchang Lu (11) , Ching-Yu Cheng (12, 13, 14) , Xueling Sim (14) , Dina Vojinovic (15) , Jennifer E. Huffman (16) , Solomon K. Musani (17) , Changwei Li (18) , Mary F. Feitosa (2) , Melissa A. Richard (3) , Raymond Noordam (19) , Jenna Baker (1) , Guanjie Chen (1) , Hugues Aschard (20, 21) , Traci M. Bartz (22) , Jingzhong Ding (23) , Rajkumar Dorajoo (24) , Alisa K. Manning (25, 7) , Tuomo Rankinen (26) , Albert V. Smith (27, 28) , Salman M. Tajuddin (1) , Wei Zhao (29) , Mariaelisa Graff (30) , Maris Alver (31) , Mathilde Boissel (32) , Jin Fang Chai (14) , Xu Chen (33) , Jasmin Divers (34) , Evangelos Evangelou (35, 36) , Chuan Gao (34) , Anuj Goel (37) , Yanick Hagemeijer (38) , Sarah E. Harris (16) , Fernando P. Hartwig (39, 40) , Meian He (41) , Andrea R. V. R. Horimoto (42) , Fang-Chi Hsu (34) , Yi-Jen Hung , Anne Jackson , Anuradhani Kasturiratne , Pirjo Komulainen , Brigitte Kühnel , Karin Leander , Keng-Hung Lin , Jian'An Luan , Leo-Pekka Lyytikäinen , Nana Matoba , Ilja Nolte , Maik Pietzner , Bram Prins , Muhammad Riaz , Antonietta Robino , M. Abdullah Said (38) , Nicole Schupf , Robert Scott , Tamar Sofer (7) , Alena Stancáková , Fumihiko Takeuchi , Bamidele Tayo , Peter van Der Most , Tibor Varga , Tzung-Dau Wang , Yajuan Wang , Erin Ware , Wanqing Wen , Yong-Bing Xiang , Lisa Yanek , Weihua Zhang , Jing Hua Zhao , Adebowale Adeyemo (1) , Saima Afaq , Najaf Amin (15) , Marzyeh Amini , Dan Arking , Zorayr Arzumanyan (9) , Tin Aung (12, 14) , Christie Ballantyne , R Graham Barr , Lawrence F. Bielak (29) , Eric Boerwinkle (3) , Erwin P. Bottinger (11) , Ulrich Broeckel , Morris Brown (5) , Brian Cade , Archie Campbell , Mickaël Canouil (32) , Sabanayagam Charumathi (12, 13) , Yii-Der Ida Chen (9) , Kaare Christensen , Maria Pina Concas , John Connell , Lisa de Las Fuentes (2) , H Janaka de Silva , Paul S. de Vries (3) , Ayo Doumatey (1) , Qing Duan , Charles Eaton , Ruben N. Eppinga (38) , Jessica Faul , James S. Floyd (22) , Nita Forouhi , Terrence Forrester , Yechiel Friedlander , Ilaria Gandin , He Gao (35) , Mohsen Ghanbari (15) , Sina Gharib , Bruna Gigante , Franco Giulianini (6) , Hans Grabe , C. Charles Gu (2) , Tamara Harris , Sami Heikkinen , Chew-Kiat Heng , Makoto Hirata , James E. Hixson (3) , M. Arfan Ikram (15) , Yucheng Jia (9) , Roby Joehanes , Craig Johnson , Jost Bruno Jonas , Anne E. Justice (30) , Tomohiro Katsuya , Chiea Chuen Khor (24) , Tuomas Kilpeläinen , Woon-Puay Koh (14) , Ivana Kolcic , Charles Kooperberg , Jose E. Krieger (42) , Stephen Kritchevsky , Michiaki Kubo , Johanna Kuusisto , Timo Lakka , Carl D. Langefeld (34) , Claudia Langenberg , Lenore Launer , Benjamin Lehne , Cora Lewis , Yize Li (2) , Jingjing Liang , Shiow Lin (2) , Ching-Ti Liu (8) , Jianjun Liu (24) , Kiang Liu , Marie Loh , Kurt K. Lohman (34) , Tin Louie , Anna Luzzi (9) , Reedik Mägi (31) , Anubha Mahajan (37) , Ani Manichaikul , Colin Mckenzie , Thomas Meitinger , Andres Metspalu (31) , Yuri Milaneschi , Lili Milani (31) , Karen Mohlke , Yukihide Momozawa , Andrew P. Morris (37) , Alison Murray , Mike Nalls , Matthias Nauck , Christopher Nelson , Kari E. North (30) , Jeffrey O'Connell , Nicholette Palmer , George Papanicolau , Nancy L. Pedersen (33) , Annette Peters , Patricia A. Peyser (29) , Ozren Polasek , Neil Poulter , Olli Raitakari , Alex Reiner , Frida Renström , Treva K. Rice (2) , Stephen Rich , Jennifer Robinson , Lynda M. Rose (6) , Frits Rosendaal , Igor Rudan , Carsten Schmidt , Pamela Schreiner , William Scott , Peter Sever , Yuan Shi (12) , Stephen Sidney , Mario Sims (17) , Jennifer A. Smith (29) , Harold Snieder , John M. Starr (16) , Konstantin Strauch , Heather Stringham , Nicholas Y. Q. Tan (12) , Hua Tang , Kent D. Taylor (9) , Yik Ying Teo (14, 24) , Yih Chung Tham (12) , Henning Tiemeier (15) , Stephen Turner , André G. Uitterlinden (15) , Diana van Heemst (19) , Melanie Waldenberger , Heming Wang (7) , Lan Wang (8) , Lihua Wang (2) , Wen Bin Wei , Christine A. Williams (2) , Gregory Wilson , Mary K. Wojczynski (2) , Jie Yao (9) , Kristin Young (30) , Caizheng Yu (41) , Jian-Min Yuan , Jie Zhou (1) , Alan Zonderman , Diane Becker , Michael Boehnke , Donald Bowden , John C. Chambers (35) , Richard Cooper , Ulf de Faire , Ian J. Deary (16) , Paul Elliott , Tõnu Esko (31) , Martin Farrall (37) , Paul Franks , Barry Freedman , Philippe Froguel (32) , Paolo Gasparini , Christian Gieger , Bernardo L. Horta (39) , Jyh-Ming Jimmy Juang , Yoichiro Kamatani , Candace Kammerer , Norihiro Kato , Jaspal Kooner , Markku Laakso , Cathy Laurie , I-Te Lee , Terho Lehtimäki , Patrik K. E. Magnusson (33) , Albertine Oldehinkel , Brenda Penninx , Alexandre C. Pereira (42) , Rainer Rauramaa , Susan Redline , Nilesh Samani , James Scott , Xiao-Ou Shu , Pim van Der Harst (38) , Lynne Wagenknecht , Jun-Sing Wang , Ya Xing Wang , Nicholas Wareham , Hugh Watkins (37) , David Weir , Ananda Wickremasinghe , Tangchun Wu (41) , Eleftheria Zeggini , Wei Zheng , Claude Bouchard (26) , Michele K. Evans (1) , Vilmundur Gudnason (27, 28) , Sharon L. R. Kardia (29) , Yongmei Liu , Bruce M. Psaty (22) , Paul M. Ridker (6, 7) , Rob M. van Dam (14) , Dennis Mook-Kanamori , Myriam Fornage (3) , Michael A. Province (2) , Tanika Kelly , Ervin Fox , Caroline Hayward (16) , Cornelia M. van Duijn (15) , E. Shyong Tai (14) , Tien Yin Wong (12, 14) , Ruth J. F. Loos (11) , Nora Franceschini (30) , Jerome I. Rotter (9) , Xiaofeng Zhu (43) , Laura J. Bierut (2) , W. James Gauderman (44) , Kenneth Rice (22) , Patricia B. Munroe (5) , Alanna C. Morrison (3) , Dabeeru C. Rao (2) , Charles N. Rotimi (1) , L. Adrienne Cupples (8)

1 NIH - National Institutes of Health [Bethesda]
2 Washington University School of Medicine in St. Louis
3 UTHealth - The University of Texas Health Science Center at Houston
4 UR - Universität Regensburg
5 QMUL - Queen Mary University of London
6 Brigham and Women's Hospital [Boston]
7 HMS - Harvard Medical School [Boston]
8 School of Public Health [Boston]
9 LA BioMed - Los Angeles Biomedical Research Institute
10 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
11 MSSM - Icahn School of Medicine at Mount Sinai [New York]
12 SERI - Singapore Eye Research Institute [Singapore]
13 Duke-NUS Medical School [Singapore]
14 NUS - National University of Singapore
15 Erasmus MC - Erasmus University Medical Center [Rotterdam]
16 University of Edinburgh
17 UMMC - University of Mississippi Medical Center
18 University of Georgia [USA]
19 Leiden University Medical Center (LUMC)
20 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
21 Harvard T.H. Chan School of Public Health
22 University of Washington [Seattle]
23 Wake Forest University
24 GIS - Genome Institute of Singapore
25 Massachusetts General Hospital [Boston]
26 Pennington Biomedical Research Center
27 IHA - Icelandic Heart Association [Kopavogur, Iceland]
28 University of Iceland [Reykjavik]
29 University of Michigan [Ann Arbor]
30 UNC - University of North Carolina [Chapel Hill]
31 University of Tartu
32 EGENODIA (GI3M) - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
33 Karolinska Institutet [Stockholm]
34 Wake Forest School of Medicine [Winston-Salem]
35 Imperial College London
36 University of Ioannina
37 University of Oxford
38 University of Groningen [Groningen]
39 UFPel - Universidade Federal de Pelotas = Federal University of Pelotas
40 University of Bristol [Bristol]
41 HUST - Huazhong University of Science and Technology [Wuhan]
42 FMUSP - Universidade de São Paulo Medical School
43 Case Western Reserve University [Cleveland]
44 USC - University of Southern California

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

Domains: Human genetics; Santé publique et épidémiologie; Methodology [stat.ME]; Applications [stat.AP]; Bioinformatics [q-bio.QM]

Amy R. Bentley, Yun J. Sung, Michael R. Brown, Thomas W. Winkler, Aldi T. Kraja, et al.. Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids. Nature Genetics, 2019, 51 (4), pp.636-648. ⟨10.1038/s41588-019-0378-y⟩. ⟨pasteur-03278554⟩