The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods

Contemp Clin Trials. 2018 Nov:74:61-69. doi: 10.1016/j.cct.2018.09.015. Epub 2018 Oct 1.

Authors

Laura M Thornton¹, Melissa A Munn-Chernoff¹, Jessica H Baker¹, Anders Juréus², Richard Parker³, Anjali K Henders⁴, Janne T Larsen⁵, Liselotte Petersen⁵, Hunna J Watson⁶, Zeynep Yilmaz¹, Katherine M Kirk³, Scott Gordon³, Virpi M Leppä², Felicity C Martin³, David C Whiteman³, Catherine M Olsen³, Thomas M Werge⁷, Nancy L Pedersen², Walter Kaye⁸, Andrew W Bergen⁹, Katherine A Halmi¹⁰, Michael Strober¹¹, Allan S Kaplan¹², D Blake Woodside¹³, James Mitchell¹⁴, Craig L Johnson¹⁵, Harry Brandt¹⁶, Steven Crawford¹⁶, L John Horwood¹⁷, Joseph M Boden¹⁷, John F Pearson¹⁷, Laramie E Duncan¹⁸, Jakob Grove⁵, Manuel Mattheisen¹⁹, Jennifer Jordan¹⁷, Martin A Kennedy¹⁷, Andreas Birgegård²⁰, Paul Lichtenstein², Claes Norring²⁰, Tracey D Wade²¹, Grant W Montgomery⁴, Nicholas G Martin³, Mikael Landén²², Preben Bo Mortensen²³, Patrick F Sullivan²⁴, Cynthia M Bulik²⁵

Affiliations

¹ University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
³ QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital QLD 4029, Australia.
⁴ The University of Queensland, Brisbane, QLD 4072, Australia.
⁵ Aarhus University, Norde Ringgade 1, 8000 Aarhus, Denmark.
⁶ University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia; Curtin University, GPO Box U1987, Perth, WA 6845, Australia.
⁷ iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Bartholin Alle 6, 8000 Aarhus, Denmark; Mental Health Services, Institute for Biological Psychiatry, MHC Sct. Hans, Kristineberg 3, 2100 Copenhagen, Denmark; University of Copenhagen, Nørregade 10, DK-1165 Copenhagen, Denmark.
⁸ University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
⁹ Biorealm Research, 6101 W Centinela Ave # 270, Culver City, CA 90230, USA; Oregon Research Institute, Eugene, OR 97403, USA.
¹⁰ Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
¹¹ University of California at Los Angeles, Los Angeles, CA 90095, USA.
¹² University of Toronto, 27 King's College Circle, Toronto, ON M5S 1A1, Canada.
¹³ University of Toronto, 27 King's College Circle, Toronto, ON M5S 1A1, Canada; Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.
¹⁴ Neuropsychiatric Research Institute, 120 8th Street South, Fargo, ND 58103, USA.
¹⁵ Eating Recovery Center, 7351 E. Lowry Blvd., Suite 200, Denver, CO 80230, USA.
¹⁶ The Center for Eating Disorders at Sheppard Pratt, 6501 N. Charles Street, Baltimore, MD 21204, USA.
¹⁷ Christchurch School of Medicine & Health Sciences, University of Otago, 2 Riccarton Avenue, PO Box 4345, Christchurch 8140, New Zealand.
¹⁸ Stanford University, 450 Serra Mall, Stanford, CA 94305-2004, USA.
¹⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden; Aarhus University, Norde Ringgade 1, 8000 Aarhus, Denmark; Stockholm Health Care Services, Stockholm County Council, Box 45436, 104 31 Stockholm, Sweden; University of Würzburg, Sanderring 2, 97070 Würzburg, Germany.
²⁰ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Box 45436, 104 31 Stockholm, Sweden.
²¹ Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia.
²² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden; Gothenburg University, Box 100, SE-405 30 Gothenburg, Sweden.
²³ Aarhus University, Norde Ringgade 1, 8000 Aarhus, Denmark; Mental Health Services, Institute for Biological Psychiatry, MHC Sct. Hans, Kristineberg 3, 2100 Copenhagen, Denmark; University of Copenhagen, Nørregade 10, DK-1165 Copenhagen, Denmark.
²⁴ University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
²⁵ University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden. Electronic address: cbulik@med.unc.edu.

Abstract

Background: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.

Methods: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H.

Results: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable.

Conclusions: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

Keywords: Anorexia nervosa; Eating disorders; Genome-wide association; Psychiatric genetics; Psychiatric genomics consortium; Social media.

Copyright © 2018. Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Anorexia Nervosa / diagnosis*
Anorexia Nervosa / genetics
Australia
Case-Control Studies
Denmark
Feeding and Eating Disorders / diagnosis
Female
Humans
Internet
Middle Aged
New Zealand
Patient Selection
Reproducibility of Results
Surveys and Questionnaires
Sweden
United States
Young Adult

Associated data

ClinicalTrials.gov/NCT01916538

Grants and funding