Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Justice, A. E. et al. (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nature Communications, 8, 14977. (doi: 10.1038/ncomms14977) (PMID:28443625) (PMCID:PMC5414044)

Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Ford, Professor Ian and Padmanabhan, Professor Sandosh and Sattar, Professor Naveed and Strawbridge, Dr Rona
• Authors: Justice, A. E., Winkler, T. W., Feitosa, M. F., Graff, M., Fisher, V. A., Young, K., Barata, L., Deng, X., Czajkowski, J., Hadley, D., Ngwa, J. S., Ahluwalia, T. S., Chu, A. Y., Heard-Costa, N. L., Lim, E., Perez, J., Eicher, J. D., Kutalik, Z., Xue, L., Mahajan, A., Renström, F., Wu, J., Qi, Q., Ahmad, S., Alfred, T., Amin, N., Bielak, L. F., Bonnefond, A., Bragg, J., Cadby, G., Chittani, M., Coggeshall, S., Corre, T., Direk, N., Eriksson, J., Fischer, K., Gorski, M., Neergaard Harder, M., Horikoshi, M., Huang, T., Huffman, J. E., Jackson, A. U., Justesen, J. M., Kanoni, S., Kinnunen, L., Kleber, M. E., Komulainen, P., Kumari, M., Lim, U., Luan, J.'a., Lyytikäinen, L.-P., Mangino, M., Manichaikul, A., Marten, J., Middelberg, R. P. S., Müller-Nurasyid, M., Navarro, P., Pérusse, L., Pervjakova, N., Sarti, C., Smith, A. V., Smith, J. A., Stančáková, A., Strawbridge, R. J., Stringham, H. M., Sung, Y. J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S. W., van der Most, P. J., Van Vliet-Ostaptchouk, J. V., Vedantam, S. L., Verweij, N., Vink, J. M., Vitart, V., Wu, Y., Yengo, L., Zhang, W., Hua Zhao, J., Zimmermann, M. E., Zubair, N., Abecasis, G. R., Adair, L. S., Afaq, S., Afzal, U., Bakker, S. J. L., Bartz, T. M., Beilby, J., Bergman, R. N., Bergmann, S., Biffar, R., Blangero, J., Boerwinkle, E., Bonnycastle, L. L., Bottinger, E., Braga, D., Buckley, B. M., Buyske, S., Campbell, H., Chambers, J. C., Collins, F. S., Curran, J. E., de Borst, G. J., de Craen, A. J. M., de Geus, E. J. C., Dedoussis, G., Delgado, G. E., den Ruijter, H. M., Eiriksdottir, G., Eriksson, A. L., Esko, T., Faul, J. D., Ford, I., Forrester, T., Gertow, K., Gigante, B., Glorioso, N., Gong, J., Grallert, H., Grammer, T. B., Grarup, N., Haitjema, S., Hallmans, G., Hamsten, A., Hansen, T., Harris, T. B., Hartman, C. A., Hassinen, M., Hastie, N. D., Heath, A. C., Hernandez, D., Hindorff, L., Hocking, L. J., Hollensted, M., Holmen, O. L., Homuth, G., Jan Hottenga, J., Huang, J., Hung, J., Hutri-Kähönen, N., Ingelsson, E., James, A. L., Jansson, J.-O., Jarvelin, M.-R., Jhun, M. A., Jørgensen, M. E., Juonala, M., Kähönen, M., Karlsson, M., Koistinen, H. A., Kolcic, I., Kolovou, G., Kooperberg, C., Krämer, B. K., Kuusisto, J., Kvaløy, K., Lakka, T. A., Langenberg, C., Launer, L. J., Leander, K., Lee, N. R., Lind, L., Lindgren, C. M., Linneberg, A., Lobbens, S., Loh, M., Lorentzon, M., Luben, R., Lubke, G., Ludolph-Donislawski, A., Lupoli, S., Madden, P. A. F., Männikkö, R., Marques-Vidal, P., Martin, N. G., McKenzie, C. A., McKnight, B., Mellström, D., Menni, C., Montgomery, G. W., Musk, A. B., Narisu, N., Nauck, M., Nolte, I. M., Oldehinkel, A. J., Olden, M., Ong, K. K., Padmanabhan, S., Peyser, P. A., Pisinger, C., Porteous, D. J., Raitakari, O. T., Rankinen, T., Rao, D. C., Rasmussen-Torvik, L. J., Rawal, R., Rice, T., Ridker, P. M., Rose, L. M., Bien, S. A., Rudan, I., Sanna, S., Sarzynski, M. A., Sattar, N., Savonen, K., Schlessinger, D., Scholtens, S., Schurmann, C., Scott, R. A., Sennblad, B., Siemelink, M. A., Silbernagel, G., Slagboom, P. E., Snieder, H., Staessen, J. A., Stott, D. J., Swertz, M. A., Swift, A. J., Taylor, K. D., Tayo, B. O., Thorand, B., Thuillier, D., Tuomilehto, J., Uitterlinden, A. G., Vandenput, L., Vohl, M.-C., Völzke, H., Vonk, J. M., Waeber, G., Waldenberger, M., Westendorp, R. G. J., Wild, S., Willemsen, G., Wolffenbuttel, B. H. R., Wong, A., Wright, A. F., Zhao, W., Zillikens, M. C., Baldassarre, D., Balkau, B., Bandinelli, S., Böger, C. A., Boomsma, D. I., Bouchard, C., Bruinenberg, M., Chasman, D. I., Chen, Y.-D., Chines, P. S., Cooper, R. S., Cucca, F., Cusi, D., Faire, U. d., Ferrucci, L., Franks, P. W., Froguel, P., Gordon-Larsen, P., Grabe, H.-J., Gudnason, V., Haiman, C. A., Hayward, C., Hveem, K., Johnson, A. D., Wouter Jukema, J., Kardia, S. L. R., Kivimaki, M., Kooner, J. S., Kuh, D., Laakso, M., Lehtimäki, T., Marchand, L. L., März, W., McCarthy, M. I., Metspalu, A., Morris, A. P., Ohlsson, C., Palmer, L. J., Pasterkamp, G., Pedersen, O., Peters, A., Peters, U., Polasek, O., Psaty, B. M., Qi, L., Rauramaa, R., Smith, B. H., Sørensen, T. I. A., Strauch, K., Tiemeier, H., Tremoli, E., van der Harst, P., Vestergaard, H., Vollenweider, P., Wareham, N. J., Weir, D. R., Whitfield, J. B., Wilson, J. F., Tyrrell, J., Frayling, T. M., Barroso, I., Boehnke, M., Deloukas, P., Fox, C. S., Hirschhorn, J. N., Hunter, D. J., Spector, T. D., Strachan, D. P., van Duijn, C. M., Heid, I. M., Mohlke, K. L., Marchini, J., Loos, R. J. F., Kilpeläinen, T. O., Liu, C.-T., Borecki, I. B., North, K. E., and Cupples, L. A.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Nature Communications 8: 14977
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
38172	1	Generation Scotland	Anna Dominiczak	Office of the Chief Scientist (CSO)	CZD/16/6	RI CARDIOVASCULAR & MEDICAL SCIENCES