Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Eating Disorders Working Group of the Psychiatric Genomics Consortium

doi:10.1016/j.biopsych.2019.04.036

Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Eating Disorders Working Group of the Psychiatric Genomics Consortium

Psychiatry & Behavioral Sciences

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

30 Scopus citations

Abstract

Background: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. Methods: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). Results: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. Conclusions: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

Original language	English (US)
Pages (from-to)	577-586
Number of pages	10
Journal	Biological psychiatry
Volume	86
Issue number	8
DOIs	https://doi.org/10.1016/j.biopsych.2019.04.036
State	Published - Oct 15 2019

Bibliographical note

Funding Information:
SY acknowledges financial support from the China Scholarship Council. JM was supported by the Wellcome Trust (Grant No. 106047). ZY was supported by the National Institutes of Health (Grant No. K01MH109782). CMB acknowledges funding from the Swedish Research Council (Grant No. 538-2013-8864). HL acknowledges financial support from the Swedish Research Council (Grant No. 2014-3831). The project has also received funding from the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Grant No. 340-2013-5867). The CATSS was supported by funding from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council. The Swedish Twin Registry is acknowledged for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under Grant No. 2017-00641. We gratefully acknowledge the contribution of the participants in the Child and Adolescent Twin Study in Sweden and their families. The following consortia provided genome-wide association study summary statistics: Psychiatric Genomics Consortium (Attention-Deficit/Hyperactivity Disorder Working Group and Eating Disorders Working Group), Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), and iPSYCH-Broad Work Group. PL has served as a speaker for Medice. CN is a consultant on a research grant from Shire. CMB has been a grant recipient from and served on scientific advisory boards for Shire and has received royalties from Pearson and Walker. HL has received educational speaking fees from Eli Lilly and Shire and has received a research grant from Shire, all outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest.

Funding Information:
SY acknowledges financial support from the China Scholarship Council . JM was supported by the Wellcome Trust (Grant No. 106047 ). ZY was supported by the National Institutes of Health (Grant No. K01MH109782 ). CMB acknowledges funding from the Swedish Research Council (Grant No. 538-2013-8864 ). HL acknowledges financial support from the Swedish Research Council (Grant No. 2014-3831 ). The project has also received funding from the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Grant No. 340-2013-5867 ). The CATSS was supported by funding from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council . The Swedish Twin Registry is acknowledged for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under Grant No. 2017-00641 .

Funding Information:
PL has served as a speaker for Medice. CN is a consultant on a research grant from Shire. CMB has been a grant recipient from and served on scientific advisory boards for Shire and has received royalties from Pearson and Walker. HL has received educational speaking fees from Eli Lilly and Shire and has received a research grant from Shire, all outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest.

Publisher Copyright:
© 2019 Society of Biological Psychiatry

Keywords

ADHD
Anorexia nervosa
Bulimia nervosa
Eating disorders
Genetic epidemiology
Polygenic risk score

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10.1016/j.biopsych.2019.04.036

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Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders : A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches. / Eating Disorders Working Group of the Psychiatric Genomics Consortium.

In: Biological psychiatry, Vol. 86, No. 8, 15.10.2019, p. 577-586.

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

@article{6e56ff0f3506428d897ffc174bae3a83,

title = "Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches",

abstract = "Background: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. Methods: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). Results: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. Conclusions: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.",

keywords = "ADHD, Anorexia nervosa, Bulimia nervosa, Eating disorders, Genetic epidemiology, Polygenic risk score",

author = "{Eating Disorders Working Group of the Psychiatric Genomics Consortium} and Shuyang Yao and Ralf Kuja-Halkola and Joanna Martin and Yi Lu and Paul Lichtenstein and Christopher H{\"u}bel and Catarina Almqvist and Magnusson, {Patrik K.} and Bulik, {Cynthia M.} and Henrik Larsson and Claes Norring and Andreas Birgeg{\aa}rd and Claes Norring and Andreas Birgeg{\aa}rd and Catarina Almqvist and Henrik Larsson and Joanna Martin and Christopher H{\"u}bel and Zeynep Yilmaz and Hunna Watson and Jessica Baker and Thornton, {Laura M.} and Bulik, {Cynthia M.} and Bulik, {Cynthia M.} and Roger Adan and Tetsuya Ando and Jessica Baker and Andrew Bergen and Wade Berrettini and Andreas Birgeg{\aa}rd and Claudette Boni and {Boraska Perica}, Vesna and Harry Brandt and Roland Burghardt and Matteo Cassina and Carolyn Cesta and Maurizio Clementi and Joni Coleman and Roger Cone and Philippe Courtet and Steven Crawford and Scott Crow and James Crowley and Unna Danner and Oliver Davis and {de Zwaan}, Martina and George Dedoussis and Daniela Degortes and Janiece DeSocio and Danielle Dick",

note = "Funding Information: SY acknowledges financial support from the China Scholarship Council. JM was supported by the Wellcome Trust (Grant No. 106047). ZY was supported by the National Institutes of Health (Grant No. K01MH109782). CMB acknowledges funding from the Swedish Research Council (Grant No. 538-2013-8864). HL acknowledges financial support from the Swedish Research Council (Grant No. 2014-3831). The project has also received funding from the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Grant No. 340-2013-5867). The CATSS was supported by funding from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council. The Swedish Twin Registry is acknowledged for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under Grant No. 2017-00641. We gratefully acknowledge the contribution of the participants in the Child and Adolescent Twin Study in Sweden and their families. The following consortia provided genome-wide association study summary statistics: Psychiatric Genomics Consortium (Attention-Deficit/Hyperactivity Disorder Working Group and Eating Disorders Working Group), Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), and iPSYCH-Broad Work Group. PL has served as a speaker for Medice. CN is a consultant on a research grant from Shire. CMB has been a grant recipient from and served on scientific advisory boards for Shire and has received royalties from Pearson and Walker. HL has received educational speaking fees from Eli Lilly and Shire and has received a research grant from Shire, all outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: SY acknowledges financial support from the China Scholarship Council . JM was supported by the Wellcome Trust (Grant No. 106047 ). ZY was supported by the National Institutes of Health (Grant No. K01MH109782 ). CMB acknowledges funding from the Swedish Research Council (Grant No. 538-2013-8864 ). HL acknowledges financial support from the Swedish Research Council (Grant No. 2014-3831 ). The project has also received funding from the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Grant No. 340-2013-5867 ). The CATSS was supported by funding from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council . The Swedish Twin Registry is acknowledged for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under Grant No. 2017-00641 . Funding Information: PL has served as a speaker for Medice. CN is a consultant on a research grant from Shire. CMB has been a grant recipient from and served on scientific advisory boards for Shire and has received royalties from Pearson and Walker. HL has received educational speaking fees from Eli Lilly and Shire and has received a research grant from Shire, all outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2019 Society of Biological Psychiatry",

year = "2019",

month = oct,

day = "15",

doi = "10.1016/j.biopsych.2019.04.036",

language = "English (US)",

volume = "86",

pages = "577--586",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier USA",

number = "8",

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TY - JOUR

T1 - Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders

T2 - A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

AU - Eating Disorders Working Group of the Psychiatric Genomics Consortium

AU - Yao, Shuyang

AU - Kuja-Halkola, Ralf

AU - Martin, Joanna

AU - Lu, Yi

AU - Lichtenstein, Paul

AU - Hübel, Christopher

AU - Almqvist, Catarina

AU - Magnusson, Patrik K.

AU - Bulik, Cynthia M.

AU - Larsson, Henrik

AU - Norring, Claes

AU - Birgegård, Andreas

AU - Norring, Claes

AU - Birgegård, Andreas

AU - Almqvist, Catarina

AU - Larsson, Henrik

AU - Martin, Joanna

AU - Hübel, Christopher

AU - Yilmaz, Zeynep

AU - Watson, Hunna

AU - Baker, Jessica

AU - Thornton, Laura M.

AU - Bulik, Cynthia M.

AU - Adan, Roger

AU - Ando, Tetsuya

AU - Baker, Jessica

AU - Bergen, Andrew

AU - Berrettini, Wade

AU - Birgegård, Andreas

AU - Boni, Claudette

AU - Boraska Perica, Vesna

AU - Brandt, Harry

AU - Burghardt, Roland

AU - Cassina, Matteo

AU - Cesta, Carolyn

AU - Clementi, Maurizio

AU - Coleman, Joni

AU - Cone, Roger

AU - Courtet, Philippe

AU - Crawford, Steven

AU - Crow, Scott

AU - Crowley, James

AU - Danner, Unna

AU - Davis, Oliver

AU - de Zwaan, Martina

AU - Dedoussis, George

AU - Degortes, Daniela

AU - DeSocio, Janiece

AU - Dick, Danielle

N1 - Funding Information: SY acknowledges financial support from the China Scholarship Council. JM was supported by the Wellcome Trust (Grant No. 106047). ZY was supported by the National Institutes of Health (Grant No. K01MH109782). CMB acknowledges funding from the Swedish Research Council (Grant No. 538-2013-8864). HL acknowledges financial support from the Swedish Research Council (Grant No. 2014-3831). The project has also received funding from the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Grant No. 340-2013-5867). The CATSS was supported by funding from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council. The Swedish Twin Registry is acknowledged for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under Grant No. 2017-00641. We gratefully acknowledge the contribution of the participants in the Child and Adolescent Twin Study in Sweden and their families. The following consortia provided genome-wide association study summary statistics: Psychiatric Genomics Consortium (Attention-Deficit/Hyperactivity Disorder Working Group and Eating Disorders Working Group), Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), and iPSYCH-Broad Work Group. PL has served as a speaker for Medice. CN is a consultant on a research grant from Shire. CMB has been a grant recipient from and served on scientific advisory boards for Shire and has received royalties from Pearson and Walker. HL has received educational speaking fees from Eli Lilly and Shire and has received a research grant from Shire, all outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: SY acknowledges financial support from the China Scholarship Council . JM was supported by the Wellcome Trust (Grant No. 106047 ). ZY was supported by the National Institutes of Health (Grant No. K01MH109782 ). CMB acknowledges funding from the Swedish Research Council (Grant No. 538-2013-8864 ). HL acknowledges financial support from the Swedish Research Council (Grant No. 2014-3831 ). The project has also received funding from the Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework (Grant No. 340-2013-5867 ). The CATSS was supported by funding from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council . The Swedish Twin Registry is acknowledged for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under Grant No. 2017-00641 . Funding Information: PL has served as a speaker for Medice. CN is a consultant on a research grant from Shire. CMB has been a grant recipient from and served on scientific advisory boards for Shire and has received royalties from Pearson and Walker. HL has received educational speaking fees from Eli Lilly and Shire and has received a research grant from Shire, all outside the submitted work. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2019 Society of Biological Psychiatry

PY - 2019/10/15

Y1 - 2019/10/15

N2 - Background: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. Methods: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). Results: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. Conclusions: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

AB - Background: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. Methods: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). Results: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. Conclusions: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

KW - ADHD

KW - Anorexia nervosa

KW - Bulimia nervosa

KW - Eating disorders

KW - Genetic epidemiology

KW - Polygenic risk score

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DO - 10.1016/j.biopsych.2019.04.036

M3 - Article

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AN - SCOPUS:85068526535

SN - 0006-3223

VL - 86

SP - 577

EP - 586

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 8

ER -

Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

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