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PMID

39533101

TITLE

Genome-wide copy number variation association study in anorexia nervosa.

ABSTRACT


This study represents the first large-scale investigation of rare (<1% population frequency) copy number variants (CNVs) in anorexia nervosa (AN). Large, rare CNVs are reported to be causally associated with anthropometric traits, neurodevelopmental disorders, and schizophrenia, yet their role in the genetic basis of AN is unclear. Using genome-wide association study (GWAS) array data from the Anorexia Nervosa Genetics Initiative (ANGI), which included 7414 AN case and 5044 controls, we investigated the association of 67 well-established syndromic CNVs and 178 pleiotropic disease-risk dosage-sensitive CNVs with AN. To identify novel CNV regions (CNVRs) that increase the risk of AN, we conducted genome-wide association studies with a focus on rare CNV-breakpoints (CNV-GWAS). We found no net enrichment of rare CNVs, either deletions or duplications, in AN, and none of the well-established syndromic or pleiotropic CNVs had a significant association with AN status. However, the CNV-GWAS found 21 nominally associated CNVRs that contribute to AN risk, covering protein-coding genes implicated in synaptic function, metabolic/mitochondrial factors, and lipid characteristics, like the CD36 (7q21.11) gene, which transports long-chain fatty acids into cells. CNVRs intersecting genes previously related to neurodevelopmental traits include deletions of NRXN1 intron 5 (2p16.3), IMMP2L (7q31.1), and PTPRD (9p23). Overall, given that our study is well powered to detect the CNV burden level reported for schizophrenia, we can conclude that rare CNVs have a limited role in the etiology of AN, as reported for bipolar disorder. Our nominal associations for the 21 discovered CNVRs are consistent with AN being a metabo-psychiatric trait, as demonstrated by the common genetic architecture of AN, and we provide association results to allow for replication in future research.
� 2024. The Author(s).

DATE PUBLISHED

2024 Nov 12

HISTORY

PUBSTATUS	PUBSTATUSDATE
received	2024/03/19
accepted	2024/10/23
revised	2024/10/20
medline	2024/11/13 13:48
pubmed	2024/11/13 13:48
entrez	2024/11/12 23:54

AUTHORS

NAME	COLLECTIVENAME	LASTNAME	FORENAME	INITIALS	AFFILIATION	AFFILIATIONINFO
Walker A		Walker	Alicia	A		Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Karlsson R		Karlsson	Robert	R		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Szatkiewicz JP		Szatkiewicz	Jin P	JP		Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thornton LM		Thornton	Laura M	LM		Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yilmaz Z		Yilmaz	Zeynep	Z		Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Leppä VM		Leppä	Virpi M	VM		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Savva A		Savva	Androula	A		Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Lin T		Lin	Tian	T		Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Sidorenko J		Sidorenko	Julia	J		Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
McRae A		McRae	Allan	A		Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Kirov G		Kirov	George	G		Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK.
Davies HL		Davies	Helena L	HL		Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Roskilde, Denmark.
Fundín BT		Fundín	Bengt T	BT		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Chawner SJRA		Chawner	Samuel J R A	SJRA		Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK.
Song J		Song	Jie	J		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Borg S		Borg	Stina	S		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Wen J		Wen	Jia	J		Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Watson HJ		Watson	Hunna J	HJ		School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
Munn-Chernoff MA		Munn-Chernoff	Melissa A	MA		Department of Community, Family, and Addiction Sciences, Texas Tech University, Lubbock, TX, USA.
Baker JH		Baker	Jessica H	JH		Equip Health Inc., Carlsbad, CA, USA.
Gordon S		Gordon	Scott	S		Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Berrettini WH		Berrettini	Wade H	WH		Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Brandt H		Brandt	Harry	H		The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA.
Crawford S		Crawford	Steven	S		The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA.
Halmi KA		Halmi	Katherine A	KA		Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
Kaplan AS		Kaplan	Allan S	AS		Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Kaye WH		Kaye	Walter H	WH		Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Mitchell J		Mitchell	James	J		Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA.
Strober M		Strober	Michael	M		David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Woodside DB		Woodside	D Blake	DB		Program for Eating Disorders, University Health Network, Toronto, ON, Canada.
Pedersen NL		Pedersen	Nancy L	NL		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Parker R		Parker	Richard	R		QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Jordan J		Jordan	Jennifer	J		Canterbury District Health Board, Christchurch, New Zealand.
Kennedy MA		Kennedy	Martin A	MA		Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
Birgegård A		Birgegård	Andreas	A		Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Landén M		Landén	Mikael	M		Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Martin NG		Martin	Nicholas G	NG		QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Sullivan PF		Sullivan	Patrick F	PF		Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Bulik CM		Bulik	Cynthia M	CM		Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. cynthia_bulik@med.unc.edu.
Wray NR		Wray	Naomi R	NR		Department of Psychiatry, University of Oxford, Oxford, UK. naomi.wray@psych.ox.ac.uk.

INVESTIGATORS

JOURNAL

VOLUME:

ISSUE:

TITLE: Molecular psychiatry

ISOABBREVIATION: Mol Psychiatry

YEAR: 2024

MONTH: Nov

DAY: 12

MEDLINEDATE:

SEASON:

CITEDMEDIUM: Internet

ISSN: 1476-5578

ISSNTYPE: Electronic

MEDLINE JOURNAL

MEDLINETA: Mol Psychiatry

COUNTRY: England

ISSNLINKING: 1359-4184

NLMUNIQUEID: 9607835

PUBLICATION TYPE

PUBLICATIONTYPE TEXT

Journal Article

COMMENTS AND CORRECTIONS

GRANTS

GRANTID	AGENCY	COUNTRY
R01MH136148; R56MH129437; R01MH120170; R01MH124871; R01MH118278; R01MH124871	U.S. Department of Health & Human Services \| NIH \| National Institute of Mental Health (NIMH)
R276-2018-4581	Lundbeckfonden (Lundbeck Foundation)

GENERAL NOTE

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