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

被引：37

作者：

Munn-Chernoff, Melissa A. ^{[1
]}

Johnson, Emma C. ^{[2
]}

Chou, Yi-Ling ^{[2
]}

Coleman, Jonathan R. I. ^{[3
,4
,5
]}

Thornton, Laura M. ^{[1
]}

Walters, Raymond K. ^{[6
,7
,8
]}

Yilmaz, Zeynep ^{[1
,9
]}

Baker, Jessica H. ^{[1
]}

Hubel, Christopher ^{[3
,10
]}

Gordon, Scott ^{[11
]}

Medland, Sarah E. ^{[11
]}

Watson, Hunna J. ^{[1
,12
,13
]}

Gaspar, Helena A. ^{[3
,4
,5
]}

Bryois, Julien ^{[10
]}

Hinney, Anke ^{[14
]}

Leppa, Virpi M. ^{[10
]}

Mattheisen, Manuel ^{[15
,16
,17
,18
]}

Ripke, Stephan ^{[6
,7
,8
,19
]}

Yao, Shuyang ^{[10
]}

Giusti-Rodriguez, Paola ^{[9
]}

Hanscombe, Ken B. ^{[20
]}

Adan, Roger A. H. ^{[21
,22
,23
]}

Alfredsson, Lars ^{[24
]}

Ando, Tetsuya ^{[25
]}

Andreassen, Ole A. ^{[26
]}

Berrettini, Wade H. ^{[27
]}

Boehm, Ilka ^{[28
]}

Boni, Claudette ^{[29
]}

Boraska Perica, Vesna ^{[30
,31
]}

Buehren, Katharina ^{[32
]}

Burghardt, Roland ^{[33
]}

Cassina, Matteo ^{[34
]}

Cichon, Sven ^{[35
,36
,37
]}

Clementi, Maurizio ^{[34
]}

Cone, Roger D. ^{[38
]}

Courtet, Philippe ^{[39
]}

Crow, Scott ^{[40
]}

Crowley, James J. ^{[9
,16
]}

Danner, Unna N. ^{[41
]}

Davis, Oliver S. P. ^{[42
,43
]}

de Zwaan, Martina ^{[44
]}

Dedoussis, George ^{[45
]}

Degortes, Daniela ^{[46
]}

DeSocio, Janiece E. ^{[47
]}

Dick, Danielle M. ^{[48
,49
,50
]}

Dikeos, Dimitris ^{[51
]}

Dina, Christian ^{[52
]}

Dmitrzak-Weglarz, Monika ^{[53
]}

Docampo, Elisa ^{[54
,55
,56
]}

Duncan, Laramie E. ^{[57
]}

机构：

[1] Univ N Carolina, Dept Psychiat, 101 Manning Dr,Campus Box 7160, Chapel Hill, NC 27515 USA

[2] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London, England

[4] Kings Coll London, Natl Inst Hlth Res Biomed Res Ctr, London, England

[5] South London & Maudsley Natl Hlth Serv Trust, London, England

[6] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[7] Harvard Med Sch, Boston, MA 02115 USA

[8] Broad Inst Massachusetts Inst Technol & Harvard U, Stanley Ctr Psychiat Res, Cambridge, MA USA

[9] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[10] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[11] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[12] Curtin Univ, Sch Psychol, Perth, WA, Australia

[13] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA, Australia

[14] Univ DuisburgEssen, Univ Hosp Essen, Dept Child & Adolescent Psychiat, Essen, Germany

[15] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[16] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden

[17] Stockholm City Council, Ctr Psychiat Res, Stockholm Hlth Care Serv, Stockholm, Sweden

[18] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany

[19] Charite, Dept Psychiat & Psychotherapy, Berlin, Germany

[20] Kings Coll London, Guys Hosp, Dept Med & Mol Genet, London, England

[21] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, Utrecht, Netherlands

[22] Altrecht Mental Hlth Inst, Ctr Eating Disorders Rintveld, Zeist, Netherlands

[23] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden

[24] Karolinska Inst, Inst Environm Med, Stockholm, Sweden

[25] Natl Inst Mental Hlth, Natl Ctr Neurol & Psychiat, Dept Behav Med, Kodaira, Japan

[26] Univ Oslo, Oslo Univ Hosp, NORMENT Ctr, Div Mental Hlth & Addict, Oslo, Oslo, Norway

[27] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA

[28] Tech Univ Dresden, Fac Med, Div Psychol & Social Med & Dev Neurosci, Dresden, Germany

[29] INSERM, Ctr Psychiat & Neurosci, U894, Paris, France

[30] Wellcome Genome Campus, Wellcome Sanger Inst, Cambridge, England

[31] Univ Split, Sch Med, Dept Med Biol, Split, Croatia

[32] Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany

[33] Klinikum Frankfurt Oder, Frankfurt, Germany

[34] Univ Padua, Dept Woman & Child Hlth, Clin Genet Unit, Padua, Italy

[35] Univ Hosp Basel, Inst Med Genet & Pathol, Basel, Switzerland

[36] Univ Basel, Dept BioMed, Basel, Switzerland

[37] Res Ctr Juelich, Inst Neurosci & Med INM1, Julich, Germany

[38] Univ Michigan, Inst Life Sci, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[39] Univ Montpellier, CHRU Montpellier, Dept Emergency Psychiat & Postacute Care, Montpellier, France

[40] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA

[41] Altrecht Mental Hlth Inst, Altrecht Eating Disorders Rintveld, Zeist, Netherlands

[42] Univ Bristol, MRC Integrative Epidemiology Unit, Bristol, England

[43] Univ Bristol, Sch Social & Community Med, Bristol, England

[44] Hannover Med Sch, Dept Psychosomat Med & Psychotherapy, Hannover, Germany

[45] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece

[46] Univ Padua, Dept Neurosci, Padua, Italy

[47] Seattle Univ, Coll Nursing, Seattle, WA 98122 USA

[48] Virginia Commonwealth Univ, Dept Psychol, Box 2018, Richmond, VA 23284 USA

[49] Virginia Commonwealth Univ, Coll Behav & Emot Hlth Inst, Richmond, VA USA

[50] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA

来源：

ADDICTION BIOLOGY | 2021年 / 26卷 / 01期

基金：

英国医学研究理事会;

关键词：

eating disorders; genetic correlation; substance use; ALCOHOL DEPENDENCE; ANOREXIA-NERVOSA; DRUG-USE; ENVIRONMENTAL CONTRIBUTIONS; BULIMIA-NERVOSA; WOMEN; GWAS; TWIN; ENDOCANNABINOIDS; COMORBIDITY;

D O I：

10.1111/adb.12880

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 similar to 2400 to similar 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.

引用

页数：20

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