Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

MA Munn-Chernoff; EC Johnson; YL Chou; JRI Coleman; LM Thornton; RK Walters; Z Yilmaz; JH Baker; C Hübel; S Gordon; SE Medland; HJ Watson; HA Gaspar; J Bryois; A Hinney; VM Leppä; M Mattheisen; S Ripke; S Yao; P Giusti-Rodríguez; KB Hanscombe; RAH Adan; L Alfredsson; T Ando; OA Andreassen; WH Berrettini; I Boehm; C Boni; V Boraska Perica; K Buehren; R Burghardt; M Cassina; S Cichon; M Clementi; RD Cone; P Courtet; S Crow; JJ Crowley; UN Danner; OS Davis; M Zwaan; G Dedoussis; D Degortes; JE DeSocio; DM Dick; D Dikeos; C Dina; M Dmitrzak-Weglarz; E Docampo; LE Duncan; K Egberts; S Ehrlich; G Escaramís; T Esko; X Estivill; A Farmer; A Favaro; F Fernández-Aranda; MM Fichter; K Fischer; M Föcker; L Foretova; AJ Forstner; M Forzan; CS Franklin; S Gallinger; I Giegling; J Giuranna; F Gonidakis; P Gorwood; M Gratacos Mayora; S Guillaume; Y Guo; H Hakonarson; K Hatzikotoulas; J Hauser; J Hebebrand; SG Helder; S Herms; B Herpertz-Dahlmann; W Herzog; LM Huckins; JI Hudson; H Imgart; H Inoko; V Janout; S Jiménez-Murcia; A Julià; G Kalsi; D Kaminská; L Karhunen; A Karwautz; MJH Kas; JL Kennedy; A Keski-Rahkonen; K Kiezebrink; YR Kim; KL Klump; GP Knudsen; MC La Via; S Le Hellard; RD Levitan; D Li; L Lilenfeld; BD Lin; J Lissowska; J Luykx; PJ Magistretti; M Maj; K Mannik; S Marsal; CR Marshall; M Mattingsdal; S McDevitt; P McGuffin; A Metspalu; I Meulenbelt; N Micali; K Mitchell; A M Monteleone; P Monteleone; B Nacmias; M Navratilova; I Ntalla; JK O'Toole; Roel Ophoff; L Padyukov; A Palotie; J Pantel; H Papezova; D Pinto; R Rabionet; A Raevuori; N Ramoz; T Reichborn-Kjennerud; V Ricca; S Ripatti; F Ritschel; M Roberts; A Rotondo; D Rujescu; F Rybakowski; P Santonastaso; A Scherag; SW Scherer; U Schmidt; NJ Schork; A Schosser; J Seitz; L Slachtova; PE Slagboom; MCT Slof-Op't Landt; A Slopien; S Sorbi; B ?wi?tkowska; JP Szatkiewicz; I Tachmazidou; E Tenconi; A Tortorella; F Tozzi; J Treasure; A Tsitsika; M Tyszkiewicz-Nwafor; K Tziouvas; AA van Elburg; EF van Furth; G Wagner; E Walton; E Widen; E Zeggini; S Zerwas; S Zipfel; AW Bergen; JM Boden; H Brandt; S Crawford; KA Halmi; LJ Horwood; C Johnson; AS Kaplan; WH Kaye; J E Mitchell; CM Olsen; JF Pearson; NL Pedersen; M Strober; T Werge; DC Whiteman; DB Woodside; J Grove; AK Henders; J T Larsen; R Parker; LV Petersen; J Jordan; MA Kennedy; A Birgegård; P Lichtenstein; C Norring; M Landén; PB Mortensen; R Polimanti; JN McClintick; AE Adkins; F Aliev; SA Bacanu; A Batzler; S Bertelsen; JM Biernacka; TB Bigdeli; L S Chen; TK Clarke; F Degenhardt; AR Docherty; AC Edwards; JC Foo; L Fox; J Frank; LM Hack; AM Hartmann; SM Hartz; S Heilmann-Heimbach; C Hodgkinson; P Hoffmann; JJ Hottenga; B Konte; J Lahti; M Lahti-Pulkkinen; D Lai; L Ligthart; A Loukola; BS Maher; H Mbarek; AM McIntosh; MB McQueen; JL Meyers; Y Milaneschi; T Palviainen; RE Peterson; E Ryu; N L Saccone; JE Salvatore; S Sanchez-Roige; M Schwandt; R Sherva; F Streit; J Strohmaier; N Thomas; JCY Wang; BT Webb; R Wedow; L Wetherill; AG Wills; H Zhou; JD Boardman; D Chen; D S Choi; WE Copeland; RC Culverhouse; N Dahmen; L Degenhardt; BW Domingue; MA Frye; W Gäebel; C Hayward; M Ising; M Keyes; F Kiefer; G Koller; J (John) Kramer; S Kuperman; S Lucae; MT Lynskey; W Maier; K Mann; S Männistö; B Müller-Myhsok; AD Murray; JI Nurnberger; U Preuss; K Räikkönen; MD Reynolds; M Ridinger; N Scherbaum; MA Schuckit; M Soyka; J Treutlein; SH Witt; N Wodarz; P Zill; DE Adkins; DI Boomsma; LJ Bierut; S Brown; KK Bucholz; EJ Costello; HJ Wit; N Diazgranados; JG Eriksson; LA Farrer; TM Foroud; NA Gillespie; AM Goate; D Goldman; RA Grucza; DB Hancock; KM Harris; V Hesselbrock; JK Hewitt; CJ Hopfer; WG Iacono; E O Johnson; VM Karpyak; KS Kendler; HR Kranzler; K Krauter; PA Lind; M McGue; J MacKillop; PA Madden; HH Maes; PKE Magnusson; EC Nelson; MM Nöthen; AA Palmer; BWJH Penninx; B Porjesz; JP Rice; M Rietschel; BP Riley; RJ Rose; PH Shen; J Silberg; MC Stallings; RE Tarter; MM Vanyukov; S Vrieze; TL Wall; JB Whitfield; H Zhao; BM Neale; TD Wade; AC Heath; GW Montgomery; NG Martin; PF Sullivan; J Kaprio; G Breen; J Gelernter; HJ Edenberg; CM Bulik; A Agrawal

doi:10.1111/adb.12880

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

MA Munn-Chernoff, EC Johnson, YL Chou, JRI Coleman, LM Thornton, RK Walters, Z Yilmaz, JH Baker, C Hübel, S Gordon, SE Medland, HJ Watson, HA Gaspar, J Bryois, A Hinney, VM Leppä, M Mattheisen, S Ripke, S Yao, P Giusti-RodríguezKB Hanscombe, RAH Adan, L Alfredsson, T Ando, OA Andreassen, WH Berrettini, I Boehm, C Boni, V Boraska Perica, K Buehren, R Burghardt, M Cassina, S Cichon, M Clementi, RD Cone, P Courtet, S Crow, JJ Crowley, UN Danner, OS Davis, M Zwaan, G Dedoussis, D Degortes, JE DeSocio, DM Dick, D Dikeos, C Dina, M Dmitrzak-Weglarz, E Docampo, LE Duncan, K Egberts, S Ehrlich, G Escaramís, T Esko, X Estivill, A Farmer, A Favaro, F Fernández-Aranda, MM Fichter, K Fischer, M Föcker, L Foretova, AJ Forstner, M Forzan, CS Franklin, S Gallinger, I Giegling, J Giuranna, F Gonidakis, P Gorwood, M Gratacos Mayora, S Guillaume, Y Guo, H Hakonarson, K Hatzikotoulas, J Hauser, J Hebebrand, SG Helder, S Herms, B Herpertz-Dahlmann, W Herzog, LM Huckins, JI Hudson, H Imgart, H Inoko, V Janout, S Jiménez-Murcia, A Julià, G Kalsi, D Kaminská, L Karhunen, A Karwautz, MJH Kas, JL Kennedy, A Keski-Rahkonen, K Kiezebrink, YR Kim, KL Klump, GP Knudsen, MC La Via, S Le Hellard, RD Levitan, D Li, L Lilenfeld, BD Lin, J Lissowska, J Luykx, PJ Magistretti, M Maj, K Mannik, S Marsal, CR Marshall, M Mattingsdal, S McDevitt, P McGuffin, A Metspalu, I Meulenbelt, N Micali, K Mitchell, A M Monteleone, P Monteleone, B Nacmias, M Navratilova, I Ntalla, JK O'Toole, Roel Ophoff, L Padyukov, A Palotie, J Pantel, H Papezova, D Pinto, R Rabionet, A Raevuori, N Ramoz, T Reichborn-Kjennerud, V Ricca, S Ripatti, F Ritschel, M Roberts, A Rotondo, D Rujescu, F Rybakowski, P Santonastaso, A Scherag, SW Scherer, U Schmidt, NJ Schork, A Schosser, J Seitz, L Slachtova, PE Slagboom, MCT Slof-Op't Landt, A Slopien, S Sorbi, B ?wi?tkowska, JP Szatkiewicz, I Tachmazidou, E Tenconi, A Tortorella, F Tozzi, J Treasure, A Tsitsika, M Tyszkiewicz-Nwafor, K Tziouvas, AA van Elburg, EF van Furth, G Wagner, E Walton, E Widen, E Zeggini, S Zerwas, S Zipfel, AW Bergen, JM Boden, H Brandt, S Crawford, KA Halmi, LJ Horwood, C Johnson, AS Kaplan, WH Kaye, J E Mitchell, CM Olsen, JF Pearson, NL Pedersen, M Strober, T Werge, DC Whiteman, DB Woodside, J Grove, AK Henders, J T Larsen, R Parker, LV Petersen, J Jordan, MA Kennedy, A Birgegård, P Lichtenstein, C Norring, M Landén, PB Mortensen, R Polimanti, JN McClintick, AE Adkins, F Aliev, SA Bacanu, A Batzler, S Bertelsen, JM Biernacka, TB Bigdeli, L S Chen, TK Clarke, F Degenhardt, AR Docherty, AC Edwards, JC Foo, L Fox, J Frank, LM Hack, AM Hartmann, SM Hartz, S Heilmann-Heimbach, C Hodgkinson, P Hoffmann, JJ Hottenga, B Konte, J Lahti, M Lahti-Pulkkinen, D Lai, L Ligthart, A Loukola, BS Maher, H Mbarek, AM McIntosh, MB McQueen, JL Meyers, Y Milaneschi, T Palviainen, RE Peterson, E Ryu, N L Saccone, JE Salvatore, S Sanchez-Roige, M Schwandt, R Sherva, F Streit, J Strohmaier, N Thomas, JCY Wang, BT Webb, R Wedow, L Wetherill, AG Wills, H Zhou, JD Boardman, D Chen, D S Choi, WE Copeland, RC Culverhouse, N Dahmen, L Degenhardt, BW Domingue, MA Frye, W Gäebel, C Hayward, M Ising, M Keyes, F Kiefer, G Koller, J (John) Kramer, S Kuperman, S Lucae, MT Lynskey, W Maier, K Mann, S Männistö, B Müller-Myhsok, AD Murray, JI Nurnberger, U Preuss, K Räikkönen, MD Reynolds, M Ridinger, N Scherbaum, MA Schuckit, M Soyka, J Treutlein, SH Witt, N Wodarz, P Zill, DE Adkins, DI Boomsma, LJ Bierut, S Brown, KK Bucholz, EJ Costello, HJ Wit, N Diazgranados, JG Eriksson, LA Farrer, TM Foroud, NA Gillespie, AM Goate, D Goldman, RA Grucza, DB Hancock, KM Harris, V Hesselbrock, JK Hewitt, CJ Hopfer, WG Iacono, E O Johnson, VM Karpyak, KS Kendler, HR Kranzler, K Krauter, PA Lind, M McGue, J MacKillop, PA Madden, HH Maes, PKE Magnusson, EC Nelson, MM Nöthen, AA Palmer, BWJH Penninx, B Porjesz, JP Rice, M Rietschel, BP Riley, RJ Rose, PH Shen, J Silberg, MC Stallings, RE Tarter, MM Vanyukov, S Vrieze, TL Wall, JB Whitfield, H Zhao, BM Neale, TD Wade, AC Heath, GW Montgomery, NG Martin, PF Sullivan, J Kaprio, G Breen, J Gelernter, HJ Edenberg, CM Bulik, A Agrawal

Psychiatry

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r_g], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r_g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r_g = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r_g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r_gs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Original language	English
Article number	e12880
Journal	Addiction Biology
Volume	26
Issue number	1
DOIs	https://doi.org/10.1111/adb.12880
Publication status	Published - Jan 2021

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Cite this

Munn-Chernoff, MA., Johnson, EC., Chou, YL., Coleman, JRI., Thornton, LM., Walters, RK., Yilmaz, Z., Baker, JH., Hübel, C., Gordon, S., Medland, SE., Watson, HJ., Gaspar, HA., Bryois, J., Hinney, A., Leppä, VM., Mattheisen, M., Ripke, S., Yao, S., ... Agrawal, A. (2021). Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies. Addiction Biology, 26(1), Article e12880. https://doi.org/10.1111/adb.12880

@article{1dcbdfe615424060b287a0600914335b,

title = "Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies",

abstract = "Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.",

author = "MA Munn-Chernoff and EC Johnson and YL Chou and JRI Coleman and LM Thornton and RK Walters and Z Yilmaz and JH Baker and C H{\"u}bel and S Gordon and SE Medland and HJ Watson and HA Gaspar and J Bryois and A Hinney and VM Lepp{\"a} and M Mattheisen and S Ripke and S Yao and P Giusti-Rodr{\'i}guez and KB Hanscombe and RAH Adan and L Alfredsson and T Ando and OA Andreassen and WH Berrettini and I Boehm and C Boni and {Boraska Perica}, V and K Buehren and R Burghardt and M Cassina and S Cichon and M Clementi and RD Cone and P Courtet and S Crow and JJ Crowley and UN Danner and OS Davis and M Zwaan and G Dedoussis and D Degortes and JE DeSocio and DM Dick and D Dikeos and C Dina and M Dmitrzak-Weglarz and E Docampo and LE Duncan and K Egberts and S Ehrlich and G Escaram{\'i}s and T Esko and X Estivill and A Farmer and A Favaro and F Fern{\'a}ndez-Aranda and MM Fichter and K Fischer and M F{\"o}cker and L Foretova and AJ Forstner and M Forzan and CS Franklin and S Gallinger and I Giegling and J Giuranna and F Gonidakis and P Gorwood and {Gratacos Mayora}, M and S Guillaume and Y Guo and H Hakonarson and K Hatzikotoulas and J Hauser and J Hebebrand and SG Helder and S Herms and B Herpertz-Dahlmann and W Herzog and LM Huckins and JI Hudson and H Imgart and H Inoko and V Janout and S Jim{\'e}nez-Murcia and A Juli{\`a} and G Kalsi and D Kaminsk{\'a} and L Karhunen and A Karwautz and MJH Kas and JL Kennedy and A Keski-Rahkonen and K Kiezebrink and YR Kim and KL Klump and GP Knudsen and {La Via}, MC and {Le Hellard}, S and RD Levitan and D Li and L Lilenfeld and BD Lin and J Lissowska and J Luykx and PJ Magistretti and M Maj and K Mannik and S Marsal and CR Marshall and M Mattingsdal and S McDevitt and P McGuffin and A Metspalu and I Meulenbelt and N Micali and K Mitchell and Monteleone, {A M} and P Monteleone and B Nacmias and M Navratilova and I Ntalla and JK O'Toole and Roel Ophoff and L Padyukov and A Palotie and J Pantel and H Papezova and D Pinto and R Rabionet and A Raevuori and N Ramoz and T Reichborn-Kjennerud and V Ricca and S Ripatti and F Ritschel and M Roberts and A Rotondo and D Rujescu and F Rybakowski and P Santonastaso and A Scherag and SW Scherer and U Schmidt and NJ Schork and A Schosser and J Seitz and L Slachtova and PE Slagboom and {Slof-Op't Landt}, MCT and A Slopien and S Sorbi and B ?wi?tkowska and JP Szatkiewicz and I Tachmazidou and E Tenconi and A Tortorella and F Tozzi and J Treasure and A Tsitsika and M Tyszkiewicz-Nwafor and K Tziouvas and {van Elburg}, AA and {van Furth}, EF and G Wagner and E Walton and E Widen and E Zeggini and S Zerwas and S Zipfel and AW Bergen and JM Boden and H Brandt and S Crawford and KA Halmi and LJ Horwood and C Johnson and AS Kaplan and WH Kaye and Mitchell, {J E} and CM Olsen and JF Pearson and NL Pedersen and M Strober and T Werge and DC Whiteman and DB Woodside and J Grove and AK Henders and Larsen, {J T} and R Parker and LV Petersen and J Jordan and MA Kennedy and A Birgeg{\aa}rd and P Lichtenstein and C Norring and M Land{\'e}n and PB Mortensen and R Polimanti and JN McClintick and AE Adkins and F Aliev and SA Bacanu and A Batzler and S Bertelsen and JM Biernacka and TB Bigdeli and Chen, {L S} and TK Clarke and F Degenhardt and AR Docherty and AC Edwards and JC Foo and L Fox and J Frank and LM Hack and AM Hartmann and SM Hartz and S Heilmann-Heimbach and C Hodgkinson and P Hoffmann and JJ Hottenga and B Konte and J Lahti and M Lahti-Pulkkinen and D Lai and L Ligthart and A Loukola and BS Maher and H Mbarek and AM McIntosh and MB McQueen and JL Meyers and Y Milaneschi and T Palviainen and RE Peterson and E Ryu and Saccone, {N L} and JE Salvatore and S Sanchez-Roige and M Schwandt and R Sherva and F Streit and J Strohmaier and N Thomas and JCY Wang and BT Webb and R Wedow and L Wetherill and AG Wills and H Zhou and JD Boardman and D Chen and Choi, {D S} and WE Copeland and RC Culverhouse and N Dahmen and L Degenhardt and BW Domingue and MA Frye and W G{\"a}ebel and C Hayward and M Ising and M Keyes and F Kiefer and G Koller and Kramer, {J (John)} and S Kuperman and S Lucae and MT Lynskey and W Maier and K Mann and S M{\"a}nnist{\"o} and B M{\"u}ller-Myhsok and AD Murray and JI Nurnberger and U Preuss and K R{\"a}ikk{\"o}nen and MD Reynolds and M Ridinger and N Scherbaum and MA Schuckit and M Soyka and J Treutlein and SH Witt and N Wodarz and P Zill and DE Adkins and DI Boomsma and LJ Bierut and S Brown and KK Bucholz and EJ Costello and HJ Wit and N Diazgranados and JG Eriksson and LA Farrer and TM Foroud and NA Gillespie and AM Goate and D Goldman and RA Grucza and DB Hancock and KM Harris and V Hesselbrock and JK Hewitt and CJ Hopfer and WG Iacono and Johnson, {E O} and VM Karpyak and KS Kendler and HR Kranzler and K Krauter and PA Lind and M McGue and J MacKillop and PA Madden and HH Maes and PKE Magnusson and EC Nelson and MM N{\"o}then and AA Palmer and BWJH Penninx and B Porjesz and JP Rice and M Rietschel and BP Riley and RJ Rose and PH Shen and J Silberg and MC Stallings and RE Tarter and MM Vanyukov and S Vrieze and TL Wall and JB Whitfield and H Zhao and BM Neale and TD Wade and AC Heath and GW Montgomery and NG Martin and PF Sullivan and J Kaprio and G Breen and J Gelernter and HJ Edenberg and CM Bulik and A Agrawal",

year = "2021",

month = jan,

doi = "10.1111/adb.12880",

language = "English",

volume = "26",

journal = "Addiction Biology",

issn = "1355-6215",

publisher = "Wiley-Blackwell",

number = "1",

}

Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, Medland, SE, Watson, HJ, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Berrettini, WH, Boehm, I, Boni, C, Boraska Perica, V, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OS, Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, Gallinger, S, Giegling, I, Giuranna, J, Gonidakis, F, Gorwood, P, Gratacos Mayora, M, Guillaume, S, Guo, Y, Hakonarson, H, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, YR, Klump, KL, Knudsen, GP, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, Mattingsdal, M, McDevitt, S, McGuffin, P, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, K, Monteleone, AM, Monteleone, P, Nacmias, B, Navratilova, M, Ntalla, I, O'Toole, JK, Ophoff, R, Padyukov, L, Palotie, A, Pantel, J, Papezova, H, Pinto, D, Rabionet, R, Raevuori, A, Ramoz, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op't Landt, MCT, Slopien, A, Sorbi, S, ?wi?tkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, JE, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Grove, J, Henders, AK, Larsen, JT, Parker, R, Petersen, LV, Jordan, J, Kennedy, MA, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Mortensen, PB, Polimanti, R, McClintick, JN, Adkins, AE, Aliev, F, Bacanu, SA, Batzler, A, Bertelsen, S, Biernacka, JM, Bigdeli, TB, Chen, LS, Clarke, TK, Degenhardt, F, Docherty, AR, Edwards, AC, Foo, JC, Fox, L, Frank, J, Hack, LM, Hartmann, AM, Hartz, SM, Heilmann-Heimbach, S, Hodgkinson, C, Hoffmann, P, Hottenga, JJ, Konte, B, Lahti, J, Lahti-Pulkkinen, M, Lai, D, Ligthart, L, Loukola, A, Maher, BS, Mbarek, H, McIntosh, AM, McQueen, MB, Meyers, JL, Milaneschi, Y, Palviainen, T, Peterson, RE, Ryu, E, Saccone, NL, Salvatore, JE, Sanchez-Roige, S, Schwandt, M, Sherva, R, Streit, F, Strohmaier, J, Thomas, N, Wang, JCY, Webb, BT, Wedow, R, Wetherill, L, Wills, AG, Zhou, H, Boardman, JD, Chen, D, Choi, DS, Copeland, WE, Culverhouse, RC, Dahmen, N, Degenhardt, L, Domingue, BW, Frye, MA, Gäebel, W, Hayward, C, Ising, M, Keyes, M, Kiefer, F, Koller, G, Kramer, J, Kuperman, S, Lucae, S, Lynskey, MT, Maier, W, Mann, K, Männistö, S, Müller-Myhsok, B, Murray, AD, Nurnberger, JI, Preuss, U, Räikkönen, K, Reynolds, MD, Ridinger, M, Scherbaum, N, Schuckit, MA, Soyka, M, Treutlein, J, Witt, SH, Wodarz, N, Zill, P, Adkins, DE, Boomsma, DI, Bierut, LJ, Brown, S, Bucholz, KK, Costello, EJ, Wit, HJ, Diazgranados, N, Eriksson, JG, Farrer, LA, Foroud, TM, Gillespie, NA, Goate, AM, Goldman, D, Grucza, RA, Hancock, DB, Harris, KM, Hesselbrock, V, Hewitt, JK, Hopfer, CJ, Iacono, WG, Johnson, EO, Karpyak, VM, Kendler, KS, Kranzler, HR, Krauter, K, Lind, PA, McGue, M, MacKillop, J, Madden, PA, Maes, HH, Magnusson, PKE, Nelson, EC, Nöthen, MM, Palmer, AA, Penninx, BWJH, Porjesz, B, Rice, JP, Rietschel, M, Riley, BP, Rose, RJ, Shen, PH, Silberg, J, Stallings, MC, Tarter, RE, Vanyukov, MM, Vrieze, S, Wall, TL, Whitfield, JB, Zhao, H, Neale, BM, Wade, TD, Heath, AC, Montgomery, GW, Martin, NG, Sullivan, PF, Kaprio, J, Breen, G, Gelernter, J, Edenberg, HJ, Bulik, CM & Agrawal, A 2021, 'Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies', Addiction Biology, vol. 26, no. 1, e12880. https://doi.org/10.1111/adb.12880

TY - JOUR

T1 - Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

AU - Munn-Chernoff, MA

AU - Johnson, EC

AU - Chou, YL

AU - Coleman, JRI

AU - Thornton, LM

AU - Walters, RK

AU - Yilmaz, Z

AU - Baker, JH

AU - Hübel, C

AU - Gordon, S

AU - Medland, SE

AU - Watson, HJ

AU - Gaspar, HA

AU - Bryois, J

AU - Hinney, A

AU - Leppä, VM

AU - Mattheisen, M

AU - Ripke, S

AU - Yao, S

AU - Giusti-Rodríguez, P

AU - Hanscombe, KB

AU - Adan, RAH

AU - Alfredsson, L

AU - Ando, T

AU - Andreassen, OA

AU - Berrettini, WH

AU - Boehm, I

AU - Boni, C

AU - Boraska Perica, V

AU - Buehren, K

AU - Burghardt, R

AU - Cassina, M

AU - Cichon, S

AU - Clementi, M

AU - Cone, RD

AU - Courtet, P

AU - Crow, S

AU - Crowley, JJ

AU - Danner, UN

AU - Davis, OS

AU - Zwaan, M

AU - Dedoussis, G

AU - Degortes, D

AU - DeSocio, JE

AU - Dick, DM

AU - Dikeos, D

AU - Dina, C

AU - Dmitrzak-Weglarz, M

AU - Docampo, E

AU - Duncan, LE

AU - Egberts, K

AU - Ehrlich, S

AU - Escaramís, G

AU - Esko, T

AU - Estivill, X

AU - Farmer, A

AU - Favaro, A

AU - Fernández-Aranda, F

AU - Fichter, MM

AU - Fischer, K

AU - Föcker, M

AU - Foretova, L

AU - Forstner, AJ

AU - Forzan, M

AU - Franklin, CS

AU - Gallinger, S

AU - Giegling, I

AU - Giuranna, J

AU - Gonidakis, F

AU - Gorwood, P

AU - Gratacos Mayora, M

AU - Guillaume, S

AU - Guo, Y

AU - Hakonarson, H

AU - Hatzikotoulas, K

AU - Hauser, J

AU - Hebebrand, J

AU - Helder, SG

AU - Herms, S

AU - Herpertz-Dahlmann, B

AU - Herzog, W

AU - Huckins, LM

AU - Hudson, JI

AU - Imgart, H

AU - Inoko, H

AU - Janout, V

AU - Jiménez-Murcia, S

AU - Julià, A

AU - Kalsi, G

AU - Kaminská, D

AU - Karhunen, L

AU - Karwautz, A

AU - Kas, MJH

AU - Kennedy, JL

AU - Keski-Rahkonen, A

AU - Kiezebrink, K

AU - Kim, YR

AU - Klump, KL

AU - Knudsen, GP

AU - La Via, MC

AU - Le Hellard, S

AU - Levitan, RD

AU - Li, D

AU - Lilenfeld, L

AU - Lin, BD

AU - Lissowska, J

AU - Luykx, J

AU - Magistretti, PJ

AU - Maj, M

AU - Mannik, K

AU - Marsal, S

AU - Marshall, CR

AU - Mattingsdal, M

AU - McDevitt, S

AU - McGuffin, P

AU - Metspalu, A

AU - Meulenbelt, I

AU - Micali, N

AU - Mitchell, K

AU - Monteleone, A M

AU - Monteleone, P

AU - Nacmias, B

AU - Navratilova, M

AU - Ntalla, I

AU - O'Toole, JK

AU - Ophoff, Roel

AU - Padyukov, L

AU - Palotie, A

AU - Pantel, J

AU - Papezova, H

AU - Pinto, D

AU - Rabionet, R

AU - Raevuori, A

AU - Ramoz, N

AU - Reichborn-Kjennerud, T

AU - Ricca, V

AU - Ripatti, S

AU - Ritschel, F

AU - Roberts, M

AU - Rotondo, A

AU - Rujescu, D

AU - Rybakowski, F

AU - Santonastaso, P

AU - Scherag, A

AU - Scherer, SW

AU - Schmidt, U

AU - Schork, NJ

AU - Schosser, A

AU - Seitz, J

AU - Slachtova, L

AU - Slagboom, PE

AU - Slof-Op't Landt, MCT

AU - Slopien, A

AU - Sorbi, S

AU - ?wi?tkowska, B

AU - Szatkiewicz, JP

AU - Tachmazidou, I

AU - Tenconi, E

AU - Tortorella, A

AU - Tozzi, F

AU - Treasure, J

AU - Tsitsika, A

AU - Tyszkiewicz-Nwafor, M

AU - Tziouvas, K

AU - van Elburg, AA

AU - van Furth, EF

AU - Wagner, G

AU - Walton, E

AU - Widen, E

AU - Zeggini, E

AU - Zerwas, S

AU - Zipfel, S

AU - Bergen, AW

AU - Boden, JM

AU - Brandt, H

AU - Crawford, S

AU - Halmi, KA

AU - Horwood, LJ

AU - Johnson, C

AU - Kaplan, AS

AU - Kaye, WH

AU - Mitchell, J E

AU - Olsen, CM

AU - Pearson, JF

AU - Pedersen, NL

AU - Strober, M

AU - Werge, T

AU - Whiteman, DC

AU - Woodside, DB

AU - Grove, J

AU - Henders, AK

AU - Larsen, J T

AU - Parker, R

AU - Petersen, LV

AU - Jordan, J

AU - Kennedy, MA

AU - Birgegård, A

AU - Lichtenstein, P

AU - Norring, C

AU - Landén, M

AU - Mortensen, PB

AU - Polimanti, R

AU - McClintick, JN

AU - Adkins, AE

AU - Aliev, F

AU - Bacanu, SA

AU - Batzler, A

AU - Bertelsen, S

AU - Biernacka, JM

AU - Bigdeli, TB

AU - Chen, L S

AU - Clarke, TK

AU - Degenhardt, F

AU - Docherty, AR

AU - Edwards, AC

AU - Foo, JC

AU - Fox, L

AU - Frank, J

AU - Hack, LM

AU - Hartmann, AM

AU - Hartz, SM

AU - Heilmann-Heimbach, S

AU - Hodgkinson, C

AU - Hoffmann, P

AU - Hottenga, JJ

AU - Konte, B

AU - Lahti, J

AU - Lahti-Pulkkinen, M

AU - Lai, D

AU - Ligthart, L

AU - Loukola, A

AU - Maher, BS

AU - Mbarek, H

AU - McIntosh, AM

AU - McQueen, MB

AU - Meyers, JL

AU - Milaneschi, Y

AU - Palviainen, T

AU - Peterson, RE

AU - Ryu, E

AU - Saccone, N L

AU - Salvatore, JE

AU - Sanchez-Roige, S

AU - Schwandt, M

AU - Sherva, R

AU - Streit, F

AU - Strohmaier, J

AU - Thomas, N

AU - Wang, JCY

AU - Webb, BT

AU - Wedow, R

AU - Wetherill, L

AU - Wills, AG

AU - Zhou, H

AU - Boardman, JD

AU - Chen, D

AU - Choi, D S

AU - Copeland, WE

AU - Culverhouse, RC

AU - Dahmen, N

AU - Degenhardt, L

AU - Domingue, BW

AU - Frye, MA

AU - Gäebel, W

AU - Hayward, C

AU - Ising, M

AU - Keyes, M

AU - Kiefer, F

AU - Koller, G

AU - Kramer, J (John)

AU - Kuperman, S

AU - Lucae, S

AU - Lynskey, MT

AU - Maier, W

AU - Mann, K

AU - Männistö, S

AU - Müller-Myhsok, B

AU - Murray, AD

AU - Nurnberger, JI

AU - Preuss, U

AU - Räikkönen, K

AU - Reynolds, MD

AU - Ridinger, M

AU - Scherbaum, N

AU - Schuckit, MA

AU - Soyka, M

AU - Treutlein, J

AU - Witt, SH

AU - Wodarz, N

AU - Zill, P

AU - Adkins, DE

AU - Boomsma, DI

AU - Bierut, LJ

AU - Brown, S

AU - Bucholz, KK

AU - Costello, EJ

AU - Wit, HJ

AU - Diazgranados, N

AU - Eriksson, JG

AU - Farrer, LA

AU - Foroud, TM

AU - Gillespie, NA

AU - Goate, AM

AU - Goldman, D

AU - Grucza, RA

AU - Hancock, DB

AU - Harris, KM

AU - Hesselbrock, V

AU - Hewitt, JK

AU - Hopfer, CJ

AU - Iacono, WG

AU - Johnson, E O

AU - Karpyak, VM

AU - Kendler, KS

AU - Kranzler, HR

AU - Krauter, K

AU - Lind, PA

AU - McGue, M

AU - MacKillop, J

AU - Madden, PA

AU - Maes, HH

AU - Magnusson, PKE

AU - Nelson, EC

AU - Nöthen, MM

AU - Palmer, AA

AU - Penninx, BWJH

AU - Porjesz, B

AU - Rice, JP

AU - Rietschel, M

AU - Riley, BP

AU - Rose, RJ

AU - Shen, PH

AU - Silberg, J

AU - Stallings, MC

AU - Tarter, RE

AU - Vanyukov, MM

AU - Vrieze, S

AU - Wall, TL

AU - Whitfield, JB

AU - Zhao, H

AU - Neale, BM

AU - Wade, TD

AU - Heath, AC

AU - Montgomery, GW

AU - Martin, NG

AU - Sullivan, PF

AU - Kaprio, J

AU - Breen, G

AU - Gelernter, J

AU - Edenberg, HJ

AU - Bulik, CM

AU - Agrawal, A

PY - 2021/1

Y1 - 2021/1

N2 - Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

AB - Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

UR - http://www.scopus.com/inward/record.url?scp=85079714981&partnerID=8YFLogxK

U2 - 10.1111/adb.12880

DO - 10.1111/adb.12880

M3 - Article

C2 - 32064741

SN - 1355-6215

VL - 26

JO - Addiction Biology

JF - Addiction Biology

IS - 1

M1 - e12880

ER -

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

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