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

Citation:

Justice AE, Winkler TW, Feitosa MF, Graff M, Fisher VA, Young K, Barata L, Deng X, Czajkowski J, Hadley D, et al. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat CommunNat CommunNat Commun. 2017;8:14977.

摘要:

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.

附注:

Justice, Anne EWinkler, Thomas WFeitosa, Mary FGraff, MisaFisher, Virginia AYoung, KristinBarata, LlildaDeng, XuanCzajkowski, JacekHadley, DavidNgwa, Julius SAhluwalia, Tarunveer SChu, Audrey YHeard-Costa, Nancy LLim, ElisePerez, JeremiahEicher, John DKutalik, ZoltanXue, LutingMahajan, AnubhaRenstrom, FridaWu, JosephQi, QibinAhmad, ShafqatAlfred, TamunoAmin, NajafBielak, Lawrence FBonnefond, AmelieBragg, JenniferCadby, GemmaChittani, MartinaCoggeshall, ScottCorre, TanguyDirek, NeseEriksson, JoelFischer, KristaGorski, MathiasNeergaard Harder, MarieHorikoshi, MomokoHuang, TaoHuffman, Jennifer EJackson, Anne UJustesen, Johanne MarieKanoni, StavroulaKinnunen, LeenaKleber, Marcus EKomulainen, PirjoKumari, MeenaLim, UnheeLuan, Jian'anLyytikainen, Leo-PekkaMangino, MassimoManichaikul, AniMarten, JonathanMiddelberg, Rita P SMuller-Nurasyid, MartinaNavarro, PauPerusse, LouisPervjakova, NataliaSarti, CinziaSmith, Albert VernonSmith, Jennifer AStancakova, AlenaStrawbridge, Rona JStringham, Heather MSung, Yun JuTanaka, ToshikoTeumer, AlexanderTrompet, Stellavan der Laan, Sander Wvan der Most, Peter JVan Vliet-Ostaptchouk, Jana VVedantam, Sailaja LVerweij, NiekVink, Jacqueline MVitart, VeroniqueWu, YingYengo, LoicZhang, WeihuaHua Zhao, JingZimmermann, Martina EZubair, NihaAbecasis, Goncalo RAdair, Linda SAfaq, SaimaAfzal, UzmaBakker, Stephan J LBartz, Traci MBeilby, JohnBergman, Richard NBergmann, SvenBiffar, ReinerBlangero, JohnBoerwinkle, EricBonnycastle, Lori LBottinger, ErwinBraga, DanieleBuckley, Brendan MBuyske, SteveCampbell, HarryChambers, John CCollins, Francis SCurran, Joanne Ede Borst, Gert Jde Craen, Anton J Mde Geus, Eco J CDedoussis, GeorgeDelgado, Graciela Eden Ruijter, Hester MEiriksdottir, GudnyEriksson, Anna LEsko, TonuFaul, Jessica DFord, IanForrester, TerrenceGertow, KarlGigante, BrunaGlorioso, NicolaGong, JianGrallert, HaraldGrammer, Tanja BGrarup, NielsHaitjema, SaskiaHallmans, GoranHamsten, AndersHansen, TorbenHarris, Tamara BHartman, Catharina AHassinen, MaijaHastie, Nicholas DHeath, Andrew CHernandez, DenaHindorff, LuciaHocking, Lynne JHollensted, MetteHolmen, Oddgeir LHomuth, GeorgJan Hottenga, JoukeHuang, JieHung, JosephHutri-Kahonen, NinaIngelsson, ErikJames, Alan LJansson, John-OlovJarvelin, Marjo-RiittaJhun, Min AJorgensen, Marit EJuonala, MarkusKahonen, MikaKarlsson, MagnusKoistinen, Heikki AKolcic, IvanaKolovou, GenovefaKooperberg, CharlesKramer, Bernhard KKuusisto, JohannaKvaloy, KirstiLakka, Timo ALangenberg, ClaudiaLauner, Lenore JLeander, KarinLee, Nanette RLind, LarsLindgren, Cecilia MLinneberg, AllanLobbens, StephaneLoh, MarieLorentzon, MattiasLuben, RobertLubke, GittaLudolph-Donislawski, AnjaLupoli, SaraMadden, Pamela A FMannikko, ReijaMarques-Vidal, PedroMartin, Nicholas GMcKenzie, Colin AMcKnight, BarbaraMellstrom, DanMenni, CristinaMontgomery, Grant WMusk, Aw BillNarisu, NarisuNauck, MatthiasNolte, Ilja MOldehinkel, Albertine JOlden, MatthiasOng, Ken KPadmanabhan, SandoshPeyser, Patricia APisinger, CharlottaPorteous, David JRaitakari, Olli TRankinen, TuomoRao, D CRasmussen-Torvik, Laura JRawal, RajeshRice, TrevaRidker, Paul MRose, Lynda MBien, Stephanie ARudan, IgorSanna, SerenaSarzynski, Mark ASattar, NaveedSavonen, KaiSchlessinger, DavidScholtens, SalomeSchurmann, ClaudiaScott, Robert ASennblad, BengtSiemelink, Marten ASilbernagel, GuntherSlagboom, P ElineSnieder, HaroldStaessen, Jan AStott, David JSwertz, Morris ASwift, Amy JTaylor, Kent DTayo, Bamidele OThorand, BarbaraThuillier, DorotheeTuomilehto, JaakkoUitterlinden, Andre GVandenput, LiesbethVohl, Marie-ClaudeVolzke, HenryVonk, Judith MWaeber, GerardWaldenberger, MelanieWestendorp, R G JWild, SarahWillemsen, GonnekeWolffenbuttel, Bruce H RWong, AndrewWright, Alan FZhao, WeiZillikens, M CarolaBaldassarre, DamianoBalkau, BeverleyBandinelli, StefaniaBoger, Carsten ABoomsma, Dorret IBouchard, ClaudeBruinenberg, MarcelChasman, Daniel IChen, Yii-DerIdaChines, Peter SCooper, Richard SCucca, FrancescoCusi, DanieleFaire, Ulf deFerrucci, LuigiFranks, Paul WFroguel, PhilippeGordon-Larsen, PennyGrabe, Hans-JorgenGudnason, VilmundurHaiman, Christopher AHayward, CarolineHveem, KristianJohnson, Andrew DWouter Jukema, JKardia, Sharon L RKivimaki, MikaKooner, Jaspal SKuh, DianaLaakso, MarkkuLehtimaki, TerhoMarchand, Loic LeMarz, WinfriedMcCarthy, Mark IMetspalu, AndresMorris, Andrew POhlsson, ClaesPalmer, Lyle JPasterkamp, GerardPedersen, OlufPeters, AnnettePeters, UlrikePolasek, OzrenPsaty, Bruce MQi, LuRauramaa, RainerSmith, Blair HSorensen, Thorkild I AStrauch, KonstantinTiemeier, HenningTremoli, Elenavan der Harst, PimVestergaard, HenrikVollenweider, PeterWareham, Nicholas JWeir, David RWhitfield, John BWilson, James FTyrrell, JessicaFrayling, Timothy MBarroso, InesBoehnke, MichaelDeloukas, PanagiotisFox, Caroline SHirschhorn, Joel NHunter, David JSpector, Tim DStrachan, David Pvan Duijn, Cornelia MHeid, Iris MMohlke, Karen LMarchini, JonathanLoos, Ruth J FKilpelainen, Tuomas OLiu, Ching-TiBorecki, Ingrid 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NIH HHS/U01 CA136792/CA/NCI NIH HHS/N01HC85080/HL/NHLBI NIH HHS/R37 CA054281/CA/NCI NIH HHS/HHSN268201100001C/WH/WHI NIH HHS/N01WH22110/WH/WHI NIH HHS/R01 DK078150/DK/NIDDK NIH HHS/HHSN268201100004C/WH/WHI NIH HHS/R01 AA013320/AA/NIAAA NIH HHS/N01HC85081/HL/NHLBI NIH HHS/R01 HL045670/HL/NHLBI NIH HHS/RG/10/12/28456/British Heart Foundation/United KingdomEnglandNat Commun. 2017 Apr 26;8:14977. doi: 10.1038/ncomms14977.