Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.
journal contribution
posted on 2019-10-17, 09:27 authored by AR Bentley, YJ Sung, MR Brown, TW Winkler, AT Kraja, I Ntalla, K Schwander, DI Chasman, E Lim, X Deng, X Guo, J Liu, Y Lu, C-Y Cheng, X Sim, D Vojinovic, JE Huffman, SK Musani, C Li, MF Feitosa, MA Richard, R Noordam, J Baker, G Chen, H Aschard, TM Bartz, J Ding, R Dorajoo, AK Manning, T Rankinen, AV Smith, SM Tajuddin, W Zhao, M Graff, M Alver, M Boissel, JF Chai, X Chen, J Divers, E Evangelou, C Gao, A Goel, Y Hagemeijer, SE Harris, FP Hartwig, M He, ARVR Horimoto, F-C Hsu, Y-J Hung, AU Jackson, A Kasturiratne, P Komulainen, B Kühnel, K Leander, K-H Lin, J Luan, L-P Lyytikäinen, N Matoba, IM Nolte, M Pietzner, B Prins, M Riaz, A Robino, MA Said, N Schupf, RA Scott, T Sofer, A Stancáková, F Takeuchi, BO Tayo, PJ van der Most, TV Varga, T-D Wang, Y Wang, EB Ware, W Wen, Y-B Xiang, LR Yanek, W Zhang, JH Zhao, A Adeyemo, S Afaq, N Amin, M Amini, DE Arking, Z Arzumanyan, T Aung, C Ballantyne, RG Barr, LF Bielak, E Boerwinkle, EP Bottinger, U Broeckel, M Brown, BE Cade, A Campbell, M Canouil, S Charumathi, Y-DI Chen, K Christensen, COGENT-Kidney Consortium, MP Concas, JM Connell, L de Las Fuentes, HJ de Silva, PS de Vries, A Doumatey, Q Duan, CB Eaton, RN Eppinga, JD Faul, JS Floyd, NG Forouhi, T Forrester, Y Friedlander, I Gandin, H Gao, M Ghanbari, SA Gharib, B Gigante, F Giulianini, HJ Grabe, CC Gu, TB Harris, S Heikkinen, C-K Heng, M Hirata, JE Hixson, MA Ikram, EPIC-InterAct Consortium, Y Jia, R Joehanes, C Johnson, JB Jonas, AE Justice, T Katsuya, CC Khor, TO Kilpeläinen, W-P Koh, I Kolcic, C Kooperberg, JE Krieger, SB Kritchevsky, M Kubo, J Kuusisto, TA Lakka, CD Langefeld, C Langenberg, LJ Launer, B Lehne, CE Lewis, Y Li, J Liang, S Lin, C-T Liu, K Liu, M Loh, KK Lohman, T Louie, A Luzzi, R Mägi, A Mahajan, AW Manichaikul, CA McKenzie, T Meitinger, A Metspalu, Y Milaneschi, L Milani, KL Mohlke, Y Momozawa, AP Morris, AD Murray, MA Nalls, M Nauck, CP Nelson, KE North, JR O'Connell, ND Palmer, GJ Papanicolau, NL Pedersen, A Peters, PA Peyser, O Polasek, N Poulter, OT Raitakari, AP Reiner, F Renström, TK Rice, SS Rich, JG Robinson, LM Rose, FR Rosendaal, I Rudan, CO Schmidt, PJ Schreiner, WR Scott, P Sever, Y Shi, S Sidney, M Sims, JA Smith, H Snieder, JM Starr, K Strauch, HM Stringham, NYQ Tan, H Tang, KD Taylor, YY Teo, YC Tham, H Tiemeier, ST Turner, AG Uitterlinden, Understanding Society Scientific Group, D van Heemst, M Waldenberger, H Wang, L Wang, WB Wei, CA Williams, G Wilson, MK Wojczynski, J Yao, K Young, C Yu, J-M Yuan, J Zhou, AB Zonderman, DM Becker, M Boehnke, DW Bowden, JC Chambers, RS Cooper, U de Faire, IJ Deary, P Elliott, T Esko, M Farrall, PW Franks, BI Freedman, P Froguel, P Gasparini, C Gieger, BL Horta, J-MJ Juang, Y Kamatani, CM Kammerer, N Kato, JS Kooner, M Laakso, CC Laurie, I-T Lee, T Lehtimäki, Lifelines Cohort, PKE Magnusson, AJ Oldehinkel, BWJH Penninx, AC Pereira, R Rauramaa, S Redline, NJ Samani, J Scott, X-O Shu, P van der Harst, LE Wagenknecht, J-S Wang, YX Wang, NJ Wareham, H Watkins, DR Weir, AR Wickremasinghe, T Wu, E Zeggini, W Zheng, C Bouchard, MK Evans, V Gudnason, SLR Kardia, Y Liu, BM Psaty, PM Ridker, RM van Dam, DO Mook-Kanamori, M Fornage, MA Province, TN Kelly, ER Fox, C Hayward, CM van Duijn, ES Tai, TY Wong, RJF Loos, N Franceschini, JI Rotter, X Zhu, LJ Bierut, WJ Gauderman, K Rice, PB Munroe, AC Morrison, DC Rao, CN Rotimi, LA CupplesThe 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.
Funding
Article Published: 29 March 2019 Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids Amy R. Bentley, Yun J. Sung, […]L. Adrienne Cupples Nature Genetics volume 51, pages636–648 (2019) | Download Citation Article metrics 3672 Accesses 4 Citations 13 Altmetric Metricsdetails Abstract 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. Access provided by University of Leicester David Wilson Library Main Levels of serum lipids, such as triglycerides and high- and low-density-lipoprotein cholesterol (HDL and LDL), are influenced by both genetic and lifestyle factors. Over 250 lipid-associated loci have been identified1,2,3,4,5,6, yet it is unclear to what extent lifestyle factors modify the effects of these variants or those of variants yet to be identified. Smoking is associated with an unfavorable lipid profile7,8, warranting its investigation as a lifestyle factor that potentially modifies genetic associations with lipids. Identifying interactions through traditional 1-degree-of-freedom (1df) tests of SNP × smoking terms may have low power, except in very large sample sizes. To enhance power, a 2-degree-of-freedom (2df) test that jointly evaluates interaction and main effects was developed9. The G
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Nature Genetics, 2019, 51 (4), pp. 636-648Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular SciencesVersion
- AM (Accepted Manuscript)
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Nature GeneticsPublisher
Nature Research (part of Springer Nature)eissn
1546-1718Acceptance date
2019-02-07Copyright date
2019Available date
2019-10-17Publisher DOI
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https://www.nature.com/articles/s41588-019-0378-yNotes
All summary results will be made available in dbGaP (phs000930.v7.p1). https://www.ncbi.nlm.nih.gov/gap/?term=phs000930.v7.p1Language
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