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

Harris TB; Tuomilehto J; Harder MN; James AL; Silbernagel G; Hutri-Kahonen N; Rudan I; Navarro P; Mahajan A; Kolcic I; Kutalik Z; Jackson AU; Balkau B; Marten J; Rankinen T; Stott DJ; Bandinelli S; Liu CT; Schlessinger D; Bien SA; Vestergaard H; Direk N; Holmen OL; van der Laan SW; Alfred T; Scholtens S; Marques-Vidal P; Olden M; Fisher VA; Hocking LJ; Kleber ME; Frayling TM; Eicher JD; Launer LJ; Lim U; Xue L; Lee NR; Lehtimaki T; Metspalu A; Rao DC; Jarvelin MR; Pervjakova N; Rasmussen-Torvik LJ; Chittani M; Strauch K; Lindgren CM; Qi L; Bergmann S; Volzke H; Heid IM; Strachan DP; Hottenga JJ; Hansen T; Haitjema S; Sorensen TIA; Kuh D; Bergman RN; Pasterkamp G; Sennblad B; McCarthy MI; Gong J; Nauck M; Bartz TM; Waeber G; Chasman DI; Strawbridge RJ; Dedoussis G; Justice AE; Wild S; Faul JD; Taylor KD; Chu AY; Hollensted M; Vedantam SL; Raitakari OT; Rauramaa R; Loh M; Eriksson J; Justesen JM; Savonen K; Cupples LA; Borecki IB; Fox CS; Hastie ND; Kivimaki M; Gudnason V; Heath AC; Narisu N; Madden PAF; Mohlke KL; Pisinger C; Wu Y; Eiriksdottir G; Barroso I; Perez J; Musk AW; Heard-Costa NL; Ludolph-Donislawski A; Lind L; Bonnycastle LL; Tyrrell J; Bragg J; Zhao W; Kvaloy K; Hassinen M; Lim E; Rice T; Hadley D; Froguel P; Winkler TW; Padmanabhan S; Gorski M; Chambers JC; Weir DR; Grabe HJ; Hirschhorn JN; Barata L; Curran JE; Campbell H; Peters U; Boehnke M; Peters A; Deng X; Langenberg C; Wilson JF; Loos RJF; de Borst GJ; Zubair N; Marchini J; Tayo BO; Afzal U; Hamsten A; Deloukas P; Hindorff L; Esko T; Chen YDI; Cusi D; Baldassarre D; Palmer LJ; Mellstrom D; Hayward C; de Faire U; Wright AF; Grallert H; Glorioso N; Scott RA; Linneberg A; Kinnunen L; Sarti C; Collins FS; Lorentzon M; Hernandez D; Spector TD; Forrester T; Schurmann C; Hung J; Luben R; Zhang WH; Grammer TB; Smith JA; Middelberg RPS; Smith BH; Oldehinkel AJ; Bielak LF; Johnson AD; Boomsma DI; Jhun MA; Vink JM; Stringham HM; Ingelsson E; Marz W; Zillikens MC; Bakker SJL; North KE; Kramer BK; Gigante B; Jansson JO; Huang J; Kooner JS; Graff M; Bonnefond A; Kardia SLR; Jorgensen ME; Kahonen M; Vonk JM; Polasek O; Ong KK; Corre T; Vollenweider P; Morris AP; Perusse L; Gertow K; Hveem K; Tiemeier H; Franks PW; Slagboom PE; Zimmermann ME; Martin NG; Sanna S; Biffar R; Bottinger E; Ohlsson C; McKnight B; Czajkowski J; Hunter DJ; Stancakova A; Horikoshi M; van der Most PJ; Verweij N; Thuillier D; Komulainen P; Ridker PM; Boerwinkle E; Peyser PA; Waldenberger M; Ferrucci L; Van Vliet-Ostaptchouk JV; Chines PS; Van der Harst P; Staessen JA; Psaty BM; Delgado GE; Rose LM; Afaq S; Eriksson AL; Hartman CA; Boger CA; Beilby J; Grarup N; Adair LS; Young K; Mannikko R; Haiman CA; van Duijn CM; Sarzynski MA; Mueller-Nurasyid M; Ford I; Manichaikul A; Huang T; Rawal R; Amin N; Westendorp RGJ; Nolte IM; Wolffenbuttel BHR; Koistinen HA; Swertz MA; Wu J; Laakso M; Smith AV; Montgomery GW; Fischer K; Willemsen G; Wong A; Le Marchand L; Leander K; Blangero J; Whitfield JB; Ahmad S; Buyske S; Menni C; Cadby G; Gordon-Larsen P; Lupoli S; Vandenput L; Kanoni S; Kumari M; Braga D; Feitosa MF; den Ruijter HM; Jukema W; Sung YJ; Bouchard C; Hallmans G; Thorand B; Abecasis GR; Karlsson M; de Craen AJM; Vitart V; Porteous DJ; Siemelink MA; Qi QB; Lobbens S; Uitterlinden AG; Kolovou G; Tanaka T; McKenzie CA; Lubke G; Kooperberg C; Snieder H; Zhao JH; Ahluwalia TS; Homuth G; Luan J; Cucca F; Renstrom F; Lyytikainen LP; Huffman JE; Teumer A; Swift AJ; Yengo L; Mangino M; Wareham NJ; Sattar N; Lakka TA; Kuusisto J; Buckley BM; Ngwa JS; Trompet S; Kilpelainen TO; Tremoli E; de Geus EJC; Pedersen O; Vohl MC; Juonala M; Cooper RS; Coggeshall S; Bruinenberg M

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

Harris TB
Tuomilehto J
Harder MN
James AL
Silbernagel G
Hutri-Kahonen N
Rudan I
Navarro P
Mahajan A
Kolcic I
Kutalik Z
Jackson AU
Balkau B
Marten J
Rankinen T
Stott DJ
Bandinelli S
Liu CT
Schlessinger D
Bien SA
Vestergaard H
Direk N
Holmen OL
van der Laan SW
Alfred T
Scholtens S
Marques-Vidal P
Olden M
Fisher VA
Hocking LJ
Kleber ME
Frayling TM
Eicher JD
Launer LJ
Lim U
Xue L
Lee NR
Lehtimaki T
Metspalu A
Rao DC
Jarvelin MR
Pervjakova N
Rasmussen-Torvik LJ
Chittani M
Strauch K
Lindgren CM
Qi L
Bergmann S
Volzke H
Heid IM
Strachan DP
Hottenga JJ
Hansen T
Haitjema S
Sorensen TIA
Kuh D
Bergman RN
Pasterkamp G
Sennblad B
McCarthy MI
Gong J
Nauck M
Bartz TM
Waeber G
Chasman DI
Strawbridge RJ
Dedoussis G
Justice AE
Wild S
Faul JD
Taylor KD
Chu AY
Hollensted M
Vedantam SL
Raitakari OT
Rauramaa R
Loh M
Eriksson J
Justesen JM
Savonen K
Cupples LA
Borecki IB
Fox CS
Hastie ND
Kivimaki M
Gudnason V
Heath AC
Narisu N
Madden PAF
Mohlke KL
Pisinger C
Wu Y
Eiriksdottir G
Barroso I
Perez J
Musk AW
Heard-Costa NL
Ludolph-Donislawski A
Lind L
Bonnycastle LL
Tyrrell J
Bragg J
Zhao W
Kvaloy K
Hassinen M
Lim E
Rice T
Hadley D
Froguel P
Winkler TW
Padmanabhan S
Gorski M
Chambers JC
Weir DR
Grabe HJ
Hirschhorn JN
Barata L
Curran JE
Campbell H
Peters U
Boehnke M
Peters A
Deng X
Langenberg C
Wilson JF
Loos RJF
de Borst GJ
Zubair N
Marchini J
Tayo BO
Afzal U
Hamsten A
Deloukas P
Hindorff L
Esko T
Chen YDI
Cusi D
Baldassarre D
Palmer LJ
Mellstrom D
Hayward C
de Faire U
Wright AF
Grallert H
Glorioso N
Scott RA
Linneberg A
Kinnunen L
Sarti C
Collins FS
Lorentzon M
Hernandez D
Spector TD
Forrester T
Schurmann C
Hung J
Luben R
Zhang WH
Grammer TB
Smith JA
Middelberg RPS
Smith BH
Oldehinkel AJ
Bielak LF
Johnson AD
Boomsma DI
Jhun MA
Vink JM
Stringham HM
Ingelsson E
Marz W
Zillikens MC
Bakker SJL
North KE
Kramer BK
Gigante B
Jansson JO
Huang J
Kooner JS
Graff M
Bonnefond A
Kardia SLR
Jorgensen ME
Kahonen M
Vonk JM
Polasek O
Ong KK
Corre T
Vollenweider P
Morris AP
Perusse L
Gertow K
Hveem K
Tiemeier H
Franks PW
Slagboom PE
Zimmermann ME
Martin NG
Sanna S
Biffar R
Bottinger E
Ohlsson C
McKnight B
Czajkowski J
Hunter DJ
Stancakova A
Horikoshi M
van der Most PJ
Verweij N
Thuillier D
Komulainen P
Ridker PM
Boerwinkle E
Peyser PA
Waldenberger M
Ferrucci L
Van Vliet-Ostaptchouk JV
Chines PS
Van der Harst P
Staessen JA
Psaty BM
Delgado GE
Rose LM
Afaq S
Eriksson AL
Hartman CA
Boger CA
Beilby J
Grarup N
Adair LS
Young K
Mannikko R
Haiman CA
van Duijn CM
Sarzynski MA
Mueller-Nurasyid M
Ford I
Manichaikul A
Huang T
Rawal R
Amin N
Westendorp RGJ
Nolte IM
Wolffenbuttel BHR
Koistinen HA
Swertz MA
Wu J
Laakso M
Smith AV
Montgomery GW
Fischer K
Willemsen G
Wong A
Le Marchand L
Leander K
Blangero J
Whitfield JB
Ahmad S
Buyske S
Menni C
Cadby G
Gordon-Larsen P
Lupoli S
Vandenput L
Kanoni S
Kumari M
Braga D
Feitosa MF
den Ruijter HM
Jukema W
Sung YJ
Bouchard C
Hallmans G
Thorand B
Abecasis GR
Karlsson M
de Craen AJM
Vitart V
Porteous DJ
Siemelink MA
Qi QB
Lobbens S
Uitterlinden AG
Kolovou G
Tanaka T
McKenzie CA
Lubke G
Kooperberg C
Snieder H
Zhao JH
Ahluwalia TS
Homuth G
Luan J
Cucca F
Renstrom F
Lyytikainen LP
Huffman JE
Teumer A
Swift AJ
Yengo L
Mangino M
Wareham NJ
Sattar N
Lakka TA
Kuusisto J
Buckley BM
Ngwa JS
Trompet S
Kilpelainen TO
Tremoli E
de Geus EJC
Pedersen O
Vohl MC
Juonala M
Cooper RS
Coggeshall S
Bruinenberg M
Katso/Avaa
Publisher's version (1.389Mb)
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NATURE PUBLISHING GROUP
doi:10.1038/ncomms14977
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042716824
Tiivistelmä
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.
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