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| PMID |
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| TITLE |
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| Leveraging transdiagnostic genetic liability to psychiatric disorders to dissect clinical outcomes of anorexia nervosa. |
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| ABSTRACT |
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| Anorexia nervosa (AN) has extensive genetic correlations with other psychiatric disorders, and genetic risk for different psychiatric disorders was associated with distinct clinical courses in AN. Uncovering associations between transdiagnostic psychiatric genetic liability and AN outcomes can facilitate its personalized treatment. In this study, we investigated the associations between transdiagnostic psychiatric genetic liability and outcomes of AN. Genomic structural equation models were fitted to genome-wide association data for AN and psychiatric disorders with high genetic correlations with AN (obsessive-compulsive symptoms [OCS], major depressive disorder [MDD], schizophrenia, and anxiety disorders) to extract one shared and five trait-specific genetic components. Next, we calculated the polygenic risk scores (PRS) for these components, including PRS , PRS , PRS , PRS , PRS and PRS , which index the shared genetic liability to all five psychiatric traits, and genetic liability specific to AN, OCS, MDD, SCZ and ANX, respectively. We then tested associations between these PRSs and clinical outcomes reported between 1997 and 2018 among AN cases from the Anorexia Nervosa Genetics Initiative (ANGI), linked to Swedish National Registers. The clinical outcomes included cumulative disease burden (i.e., number of diagnoses, medication prescriptions, and inpatient days), risks of psychiatric comorbidities, and AN symptomatology. Among 4028 included AN cases, the mean (SD) birth year was 1985 (9), and 3947 (98.0%) were female. Within AN, +1 SD increase of PRS was associated with 9-39% excess risk of disease burden and psychiatric comorbidity, whereas the associations between PRS and most clinical outcomes were statistically non-significant. +1 SD increase of PRS was associated with 3-29% increased risk of AN disease burden. Our findings show that shared psychiatric liability is associated with more adverse AN outcomes, whereas AN-specific liability is not a good indicator for its clinical course. This study provides a novel perspective on factors influencing heterogeneity in AN clinical course. |
| © 2025. The Author(s). |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2024/06/23 |
| accepted |
2025/09/10 |
| revised |
2025/08/07 |
| medline |
2025/09/23 03:17 |
| pubmed |
2025/09/23 03:17 |
| entrez |
2025/09/22 23:18 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Lu ZA |
|
Lu |
Zheng-An |
ZA |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Ploner A |
|
Ploner |
Alexander |
A |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Birgegård A |
|
Birgegård |
Andreas |
A |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
|
Eating Disorders Working Group of the Psychiatric Genomics Consortium |
|
|
|
|
|
| Landén M |
|
Landén |
Mikael |
M |
|
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. |
| Bulik CM |
|
Bulik |
Cynthia M |
CM |
|
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. |
| Bergen SE |
|
Bergen |
Sarah E |
SE |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Sarah.Bergen@ki.se. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Pedersen |
Nancy L |
NL |
|
| Yao |
Shuyang |
S |
|
| Bryois |
Julien |
J |
|
| Leppä |
Virpi M |
VM |
|
| Lichtenstein |
Paul |
P |
|
| Baker |
Jessica H |
JH |
|
| Zerwas |
Stephanie |
S |
|
| Thornton |
Laura M |
LM |
|
| La Via |
Maria C |
MC |
|
| Munn-Chernoff |
Melissa A |
MA |
|
| Lin |
Bochao Danae |
BD |
|
| Luykx |
Jurjen |
J |
|
| Adan |
Roger A H |
RAH |
|
| Danner |
Unna N |
UN |
|
| Alfredsson |
Lars |
L |
|
| Ando |
Tetsuya |
T |
|
| Andreassen |
Ole A |
OA |
|
| Mattingsdal |
Morten |
M |
|
| Aschauer |
Harald |
H |
|
| Bencko |
Vladimir |
V |
|
| Bergen |
Andrew W |
AW |
|
| Berrettini |
Wade H |
WH |
|
| Boden |
Joseph M |
JM |
|
| Horwood |
L John |
LJ |
|
| Boehm |
Ilka |
I |
|
| Ehrlich |
Stefan |
S |
|
| Franklin |
Christopher S |
CS |
|
| Tachmazidou |
Ioanna |
I |
|
| Perica |
Vesna Boraska |
VB |
|
| Crawford |
Steven |
S |
|
| Brandt |
Harry |
H |
|
| Farmer |
Anne |
A |
|
| McGuffin |
Peter |
P |
|
| Kalsi |
Gursharan |
G |
|
| Breen |
Gerome |
G |
|
| Gaspar |
Héléna A |
HA |
|
| Coleman |
Jonathan R I |
JRI |
|
| Roberts |
Marion |
M |
|
| Purves |
Kirstin L |
KL |
|
| Hanscombe |
Ken B |
KB |
|
| Burghardt |
Roland |
R |
|
| Carlberg |
Laura |
L |
|
| Clementi |
Maurizio |
M |
|
| Cassina |
Matteo |
M |
|
| Forzan |
Monica |
M |
|
| Cichon |
Sven |
S |
|
| Herms |
Stefan |
S |
|
| Forstner |
Andreas J |
AJ |
|
| Cone |
Roger D |
RD |
|
| Courtet |
Philippe |
P |
|
| Guillaume |
Sébastien |
S |
|
| Crow |
Scott |
S |
|
| Giusti-Rodríquez |
Paola |
P |
|
| Szatkiewicz |
Jin P |
JP |
|
| Crowley |
James J |
JJ |
|
| Sullivan |
Patrick F |
PF |
|
| Davis |
Oliver S P |
OSP |
|
| deZwaan |
Martina |
M |
|
| Dedoussis |
George |
G |
|
| Ntalla |
Ioanna |
I |
|
| Favaro |
Angela |
A |
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| Degortes |
Daniela |
D |
|
| Tenconi |
Elena |
E |
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| DeSocio |
Janiece E |
JE |
|
| Dick |
Danielle M |
DM |
|
| Dikeos |
Dimitris |
D |
|
| Gonidakis |
Fragiskos |
F |
|
| Dina |
Christian |
C |
|
| Dmitrzak-Weglarz |
Monika |
M |
|
| Docampo |
Elisa |
E |
|
| Escaramís |
Geòrgia |
G |
|
| Mayora |
Monica Gratacos |
MG |
|
| Duncan |
Laramie E |
LE |
|
| Duriez |
Philibert |
P |
|
| Gorwood |
Philip |
P |
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| Ramoz |
Nicolas |
N |
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| Egberts |
Karin |
K |
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| Fischer |
Krista |
K |
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| Esko |
Tõnu |
T |
|
| Espeseth |
Thomas |
T |
|
| Estivill |
Xavier |
X |
|
| Fernández-Aranda |
Fernando |
F |
|
| Jiménez-Murcia |
Susana |
S |
|
| Fichter |
Manfred M |
MM |
|
| Floyd |
James A B |
JAB |
|
| Föcker |
Manuel |
M |
|
| Foretova |
Lenka |
L |
|
| Navratilova |
Marie |
M |
|
| Gallinger |
Steven |
S |
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| Gambaro |
Giovanni |
G |
|
| Giegling |
Ina |
I |
|
| Rujescu |
Dan |
D |
|
| Gordon |
Scott |
S |
|
| Martin |
Nicholas G |
NG |
|
| Grove |
Jakob |
J |
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| Guo |
Yiran |
Y |
|
| Li |
Dong |
D |
|
| Hakonarson |
Hakon |
H |
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| Halmi |
Katherine A |
KA |
|
| Southam |
Lorraine |
L |
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| Hatzikotoulas |
Konstantinos |
K |
|
| Hauser |
Joanna |
J |
|
| Hebebrand |
Johannes |
J |
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| Peters |
Triinu |
T |
|
| Hinney |
Anke |
A |
|
| Helder |
Sietske G |
SG |
|
| Henders |
Anjali |
A |
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| Herpertz-Dahlmann |
Beate |
B |
|
| Seitz |
Jochen |
J |
|
| Herzog |
Wolfgang |
W |
|
| Hübel |
Christopher |
C |
|
| Yilmaz |
Zeynep |
Z |
|
| Xu |
Jiayi |
J |
|
| Johnson |
Jessica S |
JS |
|
| Huckins |
Laura M |
LM |
|
| Pinto |
Dalila |
D |
|
| Hudson |
James I |
JI |
|
| Imgart |
Hartmut |
H |
|
| Inoko |
Hidetoshi |
H |
|
| Janout |
Vladimir |
V |
|
| Johnson |
Craig |
C |
|
| Jordan |
Jennifer |
J |
|
| Marsal |
Sara |
S |
|
| Julià |
Antonio |
A |
|
| Papezova |
Hana |
H |
|
| Kaminská |
Deborah |
D |
|
| Kaplan |
Allan S |
AS |
|
| Kennedy |
James L |
JL |
|
| Kaprio |
Jaakko |
J |
|
| Widen |
Elisabeth |
E |
|
| Karhunen |
Leila |
L |
|
| Karwautz |
Andreas |
A |
|
| Wagner |
Gudrun |
G |
|
| Kas |
Martien J H |
MJH |
|
| Kaye |
Walter H |
WH |
|
| Kennedy |
Martin A |
MA |
|
| Keski-Rahkonen |
Anna |
A |
|
| Kiezebrink |
Kirsty |
K |
|
| Kim |
Youl-Ri |
YR |
|
| Kirk |
Katherine M |
KM |
|
| Medland |
Sarah E |
SE |
|
| Parker |
Richard |
R |
|
| Klareskog |
Lars |
L |
|
| Padyukov |
Leonid |
L |
|
| Klump |
Kelly L |
KL |
|
| Knudsen |
Gun Peggy S |
GPS |
|
| Larsen |
Janne T |
JT |
|
| Petersen |
Liselotte V |
LV |
|
| Mortensen |
Preben Bo |
PB |
|
| Le Hellard |
Stephanie |
S |
|
| Lilenfeld |
Lisa |
L |
|
| Lissowska |
Jolanta |
J |
|
| Lundervold |
Astri J |
AJ |
|
| Magistretti |
Pierre J |
PJ |
|
| Monteleone |
Alessio Maria |
AM |
|
| Maj |
Mario |
M |
|
| Mannik |
Katrin |
K |
|
| Marshall |
Christian R |
CR |
|
| Mattheisen |
Manuel |
M |
|
| McDevitt |
Sara |
S |
|
| Metspalu |
Andres |
A |
|
| Slagboom |
P Eline |
PE |
|
| Meulenbelt |
Ingrid |
I |
|
| Micali |
Nadia |
N |
|
| Mitchell |
James |
J |
|
| Mitchell |
Karen |
K |
|
| Monteleone |
Palmiero |
P |
|
| Montgomery |
Grant W |
GW |
|
| Nacmias |
Benedetta |
B |
|
| Sorbi |
Sandro |
S |
|
| Whiteman |
David C |
DC |
|
| Olsen |
Catherine M |
CM |
|
| Ophoff |
Roel A |
RA |
|
| O'Toole |
Julie |
J |
|
| Palotie |
Aarno |
A |
|
| Pantel |
Jacques |
J |
|
| Pearson |
John F |
JF |
|
| Raevuori |
Anu |
A |
|
| Reichborn-Kjennerud |
Ted |
T |
|
| Ricca |
Valdo |
V |
|
| Ripatti |
Samuli |
S |
|
| Ripke |
Stephan |
S |
|
| Rotondo |
Alessandro |
A |
|
| Rybakowski |
Filip |
F |
|
| Santonastaso |
Paolo |
P |
|
| Scherag |
André |
A |
|
| Scherer |
Stephen W |
SW |
|
| Schmidt |
Ulrike |
U |
|
| Treasure |
Janet |
J |
|
| Schork |
Nicholas J |
NJ |
|
| Schosser |
Alexandra |
A |
|
| Slachtova |
Lenka |
L |
|
| Slof-Op't |
Margarita C T |
MCT |
|
| van Furth |
Eric F |
EF |
|
| Tyszkiewicz-Nwafor |
Marta |
M |
|
| Slopien |
Agnieszka |
A |
|
| Soranzo |
Nicole |
N |
|
| Steen |
Vidar W |
VW |
|
| Strober |
Michael |
M |
|
| Stuber |
Garret D |
GD |
|
| Świątkowska |
Beata |
B |
|
| Tam |
Friederike I |
FI |
|
| Tortorella |
Alfonso |
A |
|
| Tozzi |
Federica |
F |
|
| Tsitsika |
Artemis |
A |
|
| Tziouvas |
Konstantinos |
K |
|
| van Elburg |
Annemarie |
A |
|
| Wade |
Tracey D |
TD |
|
| Watson |
Hunna J |
HJ |
|
| Werge |
Thomas |
T |
|
| Wichmann |
H-Erich |
HE |
|
| Woodside |
D Blake |
DB |
|
| Zeggini |
Eleftheria |
E |
|
| Zipfel |
Stephan |
S |
|
| Maguire |
Sarah L |
SL |
|
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| JOURNAL |
|
| VOLUME: |
| ISSUE: |
| TITLE: Molecular psychiatry |
| ISOABBREVIATION: Mol Psychiatry |
| YEAR: 2025 |
| MONTH: Sep |
| DAY: 23 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1476-5578 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Mol Psychiatry |
| COUNTRY: England |
| ISSNLINKING: 1359-4184 |
| NLMUNIQUEID: 9607835 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 2021-03126 |
Vetenskapsrådet (Swedish Research Council) |
|
| 538-2013-8864 |
Vetenskapsrådet (Swedish Research Council) |
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| R56MH129437 |
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) |
|
| R01MH120170 |
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) |
|
| R01MH124871 |
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) |
|
| R01MH119084 |
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) |
|
| R01MH124871 |
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) |
|
| R276-2018-4581 |
Lundbeckfonden (Lundbeck Foundation) |
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| GENERAL NOTE |
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| CHEMICALS |
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