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

Eating Disorders Working Group of the PsychiatricGenomics Consortium (PGC-ED)

doi:10.1111/adb.12880

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

Eating Disorders Working Group of the PsychiatricGenomics Consortium (PGC-ED)

University of North Carolina at Chapel Hill

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

28 Citations (Scopus)

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.

Original language	English
Article number	e12880
Number of pages	20
Journal	Addiction Biology
Volume	26
Issue number	1
Early online date	16 Feb 2020
DOIs	https://doi.org/10.1111/adb.12880
Publication status	Published - Jan 2021

Bibliographical note

Funding Information:
Grant support for individual authors can be found in Table S10. This study included summary statistics of a genetic study on cannabis use (Pasman et al [2018] Nature Neuroscience). We would like to acknowledge all participating groups of the International Cannabis Consortium, and in particular, the members of the working group including Joelle Pasman, Karin Verweij, Nathan Gillespie, Eske Derks, and Jacqueline Vink. Pasman et al (2018) included data from the UK Biobank resource under application numbers 9905, 16406, and 25331. We thank all study volunteers, study coordinators, and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative was an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS) and the Carolina Data Warehouse. PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children's Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case-Control Consortium-3 (WTCCC-3), the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), the QSkin Sun and Health Study, Riks?t (Swedish National Quality Register for Eating Disorders), the Stockholm Center for Eating Disorders (SC?), LifeGene, the UK Biobank, and all PGC-ED members for their support in providing individual samples used in this study. We thank SURFsara (http://www.surf.nl) for support in using the Lisa Compute Cluster. We thank Max Lam, Institute of Mental Health, Singapore, for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was supported by the National Institute of Mental Health of the US National Institutes of Health under Award Number U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. The PGC-SUD receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532. We gratefully acknowledge prior support from the National Institute on Alcohol Abuse and Alcoholism. Statistical analyses for the PGC were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Cohort specific acknowledgements may be found in Walters et al (2018) Nature Neuroscience.

Publisher Copyright:
© 2020 Society for the Study of Addiction

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Data Availability Statement

Data Access: This manuscript was a joint collaboration between the Eating Disorders and Substance Use Disorders Working Groups of the Psychiatric Genomics Consortium. These data can be found at https://www.med.unc.edu/pgc/data-index/. Additional datasets included in this study were obtained multiple ways. We recieved summary statistics directly from the first author of the primary GWAS manuscript for the bulimia nervosa factor score (Australian Twin Registry), alcohol use disorder (Million Veteran Program), nicotine dependence (multiple samples), and cannabis initiation (International Cannabis Consortium and UK Biobank). Summary statistics for drinks per week, smoking initiation, smoking cessation, and cigarettes per day (GSCAN) were downloaded from https://conservancy.umn.edu/handle/11299/201564 on 7 March 2019. Summary statistics for cannabis use disorder (iPSYCH) were downloaded from https://ipsych.dk/forskning/downloads/ on 27 June 2019.

Supporting information: Additional supporting information may be found online in the Supporting Information section at the end of this article.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/adb.12880Licence: Unspecified

Cite this

@article{ecd4c4a0c7de4b6eaee65f82261b715d,

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. ",

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

author = "{Eating Disorders Working Group of the PsychiatricGenomics Consortium (PGC-ED)} and Munn-Chernoff, {Melissa A.} and Kirsty Kiezebrink",

note = "Funding Information: Grant support for individual authors can be found in Table S10. This study included summary statistics of a genetic study on cannabis use (Pasman et al [2018] Nature Neuroscience). We would like to acknowledge all participating groups of the International Cannabis Consortium, and in particular, the members of the working group including Joelle Pasman, Karin Verweij, Nathan Gillespie, Eske Derks, and Jacqueline Vink. Pasman et al (2018) included data from the UK Biobank resource under application numbers 9905, 16406, and 25331. We thank all study volunteers, study coordinators, and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative was an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS) and the Carolina Data Warehouse. PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children's Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case-Control Consortium-3 (WTCCC-3), the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), the QSkin Sun and Health Study, Riks?t (Swedish National Quality Register for Eating Disorders), the Stockholm Center for Eating Disorders (SC?), LifeGene, the UK Biobank, and all PGC-ED members for their support in providing individual samples used in this study. We thank SURFsara (http://www.surf.nl) for support in using the Lisa Compute Cluster. We thank Max Lam, Institute of Mental Health, Singapore, for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was supported by the National Institute of Mental Health of the US National Institutes of Health under Award Number U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. The PGC-SUD receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532. We gratefully acknowledge prior support from the National Institute on Alcohol Abuse and Alcoholism. Statistical analyses for the PGC were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Cohort specific acknowledgements may be found in Walters et al (2018) Nature Neuroscience. Publisher Copyright: {\textcopyright} 2020 Society for the Study of Addiction Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2021",

month = jan,

doi = "10.1111/adb.12880",

language = "English",

volume = "26",

journal = "Addiction Biology",

issn = "1355-6215",

publisher = "Wiley-Blackwell",

number = "1",

}

TY - JOUR

T1 - Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes

T2 - Evidence from genome‐wide association studies

AU - Eating Disorders Working Group of the PsychiatricGenomics Consortium (PGC-ED)

AU - Munn-Chernoff, Melissa A.

AU - Kiezebrink, Kirsty

N1 - Funding Information: Grant support for individual authors can be found in Table S10. This study included summary statistics of a genetic study on cannabis use (Pasman et al [2018] Nature Neuroscience). We would like to acknowledge all participating groups of the International Cannabis Consortium, and in particular, the members of the working group including Joelle Pasman, Karin Verweij, Nathan Gillespie, Eske Derks, and Jacqueline Vink. Pasman et al (2018) included data from the UK Biobank resource under application numbers 9905, 16406, and 25331. We thank all study volunteers, study coordinators, and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative was an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS) and the Carolina Data Warehouse. PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children's Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case-Control Consortium-3 (WTCCC-3), the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), the QSkin Sun and Health Study, Riks?t (Swedish National Quality Register for Eating Disorders), the Stockholm Center for Eating Disorders (SC?), LifeGene, the UK Biobank, and all PGC-ED members for their support in providing individual samples used in this study. We thank SURFsara (http://www.surf.nl) for support in using the Lisa Compute Cluster. We thank Max Lam, Institute of Mental Health, Singapore, for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was supported by the National Institute of Mental Health of the US National Institutes of Health under Award Number U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. The PGC-SUD receives support from the National Institute on Drug Abuse and the National Institute of Mental Health via MH109532. We gratefully acknowledge prior support from the National Institute on Alcohol Abuse and Alcoholism. Statistical analyses for the PGC were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Cohort specific acknowledgements may be found in Walters et al (2018) Nature Neuroscience. Publisher Copyright: © 2020 Society for the Study of Addiction Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

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.

KW - eating disorders

KW - genetic correlation

KW - substance use

KW - DRUG-USE

KW - GWAS

KW - BULIMIA-NERVOSA

KW - TWIN

KW - COMORBIDITY

KW - WOMEN

KW - ANOREXIA-NERVOSA

KW - ENDOCANNABINOIDS

KW - ENVIRONMENTAL CONTRIBUTIONS

KW - ALCOHOL DEPENDENCE

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

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this