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| PMID |
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| TITLE |
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| A cross-disorder analysis of CNVs finds novel loci and dose-dependent relationships of genes to psychiatric traits. |
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| ABSTRACT |
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| Rare copy number variants (CNVs) are a key component of the genetic basis of psychiatric conditions, but have not been well characterized for most. We conducted a genome-wide CNV analysis across six diagnostic categories (N = 574,965): autism (ASD), ADHD, bipolar disorder (BD), major depressive disorder (MDD), PTSD, and schizophrenia (SCZ). We identified 35 genome-wide significant associations at 18 loci, including novel associations in SCZ ( - ) and in the combined cross-disorder analysis ( ). Rare CNVs accounted for 1-3% of heritability across diagnoses. In ASD, associations were uniformly positive, consistent with autism having diverse etiologies and clinical presentations. By contrast, CNVs showed a dose-dependent relationship for other diagnoses, including SCZ and PTSD, with reciprocal deletions and duplications having inversely correlated effects and distinct genotype-phenotype relationships. Our findings suggest that genes have effects that are both dose-dependent and pleiotropic, such that a positive influence on one dimension of psychopathology may be accompanied by positive or negative effects on others. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| medline |
2025/08/12 06:28 |
| pubmed |
2025/08/12 06:27 |
| entrez |
2025/08/12 05:16 |
| pmc-release |
2025/08/11 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Shanta O |
|
Shanta |
Omar |
O |
|
|
| Klein M |
|
Klein |
Marieke |
M |
|
|
| Sacks M |
|
Sacks |
Molly |
M |
|
|
| MacDonald JR |
|
MacDonald |
Jeffrey R |
JR |
|
|
| Maihofer A |
|
Maihofer |
Adam |
A |
|
|
| Ahangari M |
|
Ahangari |
Mohammad |
M |
|
|
| Engchuan W |
|
Engchuan |
Worrawat |
W |
|
|
| Thiruvahindrapuram B |
|
Thiruvahindrapuram |
Bhooma |
B |
|
|
| Guevara J |
|
Guevara |
James |
J |
|
|
| Hong O |
|
Hong |
Oanh |
O |
|
|
| Huguet G |
|
Huguet |
Guillaume |
G |
|
|
| Sønderby I |
|
Sønderby |
Ida |
I |
|
|
| Kalyuzhny M |
|
Kalyuzhny |
Maria |
M |
|
|
| Adams MJ |
|
Adams |
Mark J |
MJ |
|
|
| Adolfsson R |
|
Adolfsson |
Rolf |
R |
|
|
| Agartz I |
|
Agartz |
Ingrid |
I |
|
|
| Aiello AE |
|
Aiello |
Allison E |
AE |
|
|
| Alda M |
|
Alda |
Martin |
M |
|
|
| Allardyce J |
|
Allardyce |
Judith |
J |
|
|
| Amstadter AB |
|
Amstadter |
Ananda B |
AB |
|
|
| Andlauer TFM |
|
Andlauer |
Till F M |
TFM |
|
|
| Andreassen OA |
|
Andreassen |
Ole A |
OA |
|
|
| Artigas MS |
|
Artigas |
María S |
MS |
|
|
| Austin SB |
|
Austin |
S Bryn |
SB |
|
|
| Ayub M |
|
Ayub |
Muhammad |
M |
|
|
| Baker DG |
|
Baker |
Dewleen G |
DG |
|
|
| Bass N |
|
Bass |
Nick |
N |
|
|
| Baune BT |
|
Baune |
Bernhard T |
BT |
|
|
| Bayas M |
|
Bayas |
Maximilian |
M |
|
|
| Berger K |
|
Berger |
Klaus |
K |
|
|
| Biernacka JM |
|
Biernacka |
Joanna M |
JM |
|
|
| Bigdeli T |
|
Bigdeli |
Tim |
T |
|
|
| Bisson JI |
|
Bisson |
Jonathan I |
JI |
|
|
| Blackwood D |
|
Blackwood |
Douglas |
D |
|
|
| Boks M |
|
Boks |
Marco |
M |
|
|
| Braff D |
|
Braff |
David |
D |
|
|
| Bramon E |
|
Bramon |
Elvira |
E |
|
|
| Breen G |
|
Breen |
Gerome |
G |
|
|
| Brueckl T |
|
Brueckl |
Tanja |
T |
|
|
| Bryant RA |
|
Bryant |
Richard A |
RA |
|
|
| Bulik CM |
|
Bulik |
Cynthia M |
CM |
|
|
| Buxbaum J |
|
Buxbaum |
Joseph |
J |
|
|
| Cairns MJ |
|
Cairns |
Murray J |
MJ |
|
|
| Caldas-de-Almeida JM |
|
Caldas-de-Almeida |
Jose M |
JM |
|
|
| Campbell M |
|
Campbell |
Megan |
M |
|
|
| Campion D |
|
Campion |
Dominique |
D |
|
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| Carr VJ |
|
Carr |
Vaughan J |
VJ |
|
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| Castelao E |
|
Castelao |
Enrique |
E |
|
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| Chaumette B |
|
Chaumette |
Boris |
B |
|
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| Cichon S |
|
Cichon |
Sven |
S |
|
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| Cohen D |
|
Cohen |
David |
D |
|
|
| Corvin A |
|
Corvin |
Aiden |
A |
|
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| Craddock N |
|
Craddock |
Nicholas |
N |
|
|
| Crosbie J |
|
Crosbie |
Jennifer |
J |
|
|
| Czamara D |
|
Czamara |
Darrina |
D |
|
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| Dannlowski U |
|
Dannlowski |
Udo |
U |
|
|
| Degenhardt F |
|
Degenhardt |
Franziska |
F |
|
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| Delahanty DL |
|
Delahanty |
Douglas L |
DL |
|
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| Dempfle A |
|
Dempfle |
Astrid |
A |
|
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| Desachy G |
|
Desachy |
Guillaume |
G |
|
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| Di Florio A |
|
Di Florio |
Arianna |
A |
|
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| Dickerson FB |
|
Dickerson |
Faith B |
FB |
|
|
| Djurovic S |
|
Djurovic |
Srdjan |
S |
|
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| Domschke K |
|
Domschke |
Katharina |
K |
|
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| Douglas L |
|
Douglas |
Lisa |
L |
|
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| Drange OK |
|
Drange |
Ole K |
OK |
|
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| Duncan LE |
|
Duncan |
Laramie E |
LE |
|
|
| Edenberg HJ |
|
Edenberg |
Howard J |
HJ |
|
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| Esko T |
|
Esko |
Tonu |
T |
|
|
| Faraone S |
|
Faraone |
Steve |
S |
|
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| Feeny NC |
|
Feeny |
Norah C |
NC |
|
|
| Forstner AJ |
|
Forstner |
Andreas J |
AJ |
|
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| Franke B |
|
Franke |
Barbara |
B |
|
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| Frye M |
|
Frye |
Mark |
M |
|
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| Fu DJ |
|
Fu |
Dong-Jing |
DJ |
|
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| Fullerton JM |
|
Fullerton |
Janice M |
JM |
|
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| Gareeva A |
|
Gareeva |
Anna |
A |
|
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| Garvert L |
|
Garvert |
Linda |
L |
|
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| Gatt JM |
|
Gatt |
Justine M |
JM |
|
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| Gejman P |
|
Gejman |
Pablo |
P |
|
|
| Geschwind DH |
|
Geschwind |
Daniel H |
DH |
|
|
| Giegling I |
|
Giegling |
Ina |
I |
|
|
| Glatt SJ |
|
Glatt |
Stephen J |
SJ |
|
|
| Glessner J |
|
Glessner |
Joe |
J |
|
|
| Goes FS |
|
Goes |
Fernando S |
FS |
|
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| Gordon-Smith K |
|
Gordon-Smith |
Katherine |
K |
|
|
| Grabe H |
|
Grabe |
Hans |
H |
|
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| Green MJ |
|
Green |
Melissa J |
MJ |
|
|
| Green MF |
|
Green |
Michael F |
MF |
|
|
| Greenwood T |
|
Greenwood |
Tiffany |
T |
|
|
| Grigoroiu-Serbanescu M |
|
Grigoroiu-Serbanescu |
Maria |
M |
|
|
| Gur RE |
|
Gur |
Raquel E |
RE |
|
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| Gur RC |
|
Gur |
Ruben C |
RC |
|
|
| Guzman-Parra J |
|
Guzman-Parra |
Jose |
J |
|
|
| Haavik J |
|
Haavik |
Jan |
J |
|
|
| Hahn T |
|
Hahn |
Tim |
T |
|
|
| Hakonarson H |
|
Hakonarson |
Hakon |
H |
|
|
| Hallmayer J |
|
Hallmayer |
Joachim |
J |
|
|
| Hamshere ML |
|
Hamshere |
Marian L |
ML |
|
|
| Hartmann AM |
|
Hartmann |
Annette M |
AM |
|
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| Hassan A |
|
Hassan |
Arsalan |
A |
|
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| Hayward C |
|
Hayward |
Caroline |
C |
|
|
| Hebebrand J |
|
Hebebrand |
Johannes |
J |
|
|
| Hemmings SMJ |
|
Hemmings |
Sian M J |
SMJ |
|
|
| Herms S |
|
Herms |
Stefan |
S |
|
|
| Herrera-Rivero M |
|
Herrera-Rivero |
Marisol |
M |
|
|
| Hinney A |
|
Hinney |
Anke |
A |
|
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| Homuth G |
|
Homuth |
Georg |
G |
|
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| Ingason A |
|
Ingason |
Andrés |
A |
|
|
| Ito LT |
|
Ito |
Lucas T |
LT |
|
|
| Iwata N |
|
Iwata |
Nakao |
N |
|
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| Jones I |
|
Jones |
Ian |
I |
|
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| Jones LA |
|
Jones |
Lisa A |
LA |
|
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| Jonsson L |
|
Jonsson |
Lina |
L |
|
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| Jönsson EG |
|
Jönsson |
Erik G |
EG |
|
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| Kahn RS |
|
Kahn |
René S |
RS |
|
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| Karlsson R |
|
Karlsson |
Robert |
R |
|
|
| Kaufman ML |
|
Kaufman |
Milissa L |
ML |
|
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| Kelsoe JR |
|
Kelsoe |
John R |
JR |
|
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| Kennedy JL |
|
Kennedy |
James L |
JL |
|
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| King A |
|
King |
Anthony |
A |
|
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| Kircher T |
|
Kircher |
Tilo |
T |
|
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| Kirov G |
|
Kirov |
George |
G |
|
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| Knappskog P |
|
Knappskog |
Per |
P |
|
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| Knowles JA |
|
Knowles |
James A |
JA |
|
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| Kobayashi N |
|
Kobayashi |
Nene |
N |
|
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| Koenen KC |
|
Koenen |
Karestan C |
KC |
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| Konte B |
|
Konte |
Bettina |
B |
|
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| Korgaonkar M |
|
Korgaonkar |
Mayuresh |
M |
|
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| Kowalec K |
|
Kowalec |
Kaarina |
K |
|
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| Krebs MO |
|
Krebs |
Marie-Odile |
MO |
|
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| Landén M |
|
Landén |
Mikael |
M |
|
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| Laurent-Levinson C |
|
Laurent-Levinson |
Claudine |
C |
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| Lebois LA |
|
Lebois |
Lauren A |
LA |
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| Levinson D |
|
Levinson |
Doug |
D |
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| Lewis C |
|
Lewis |
Cathryn |
C |
|
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| Li Q |
|
Li |
Qingqin |
Q |
|
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| Liberzon I |
|
Liberzon |
Israel |
I |
|
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| Light G |
|
Light |
Greg |
G |
|
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| Loo SK |
|
Loo |
Sandra K |
SK |
|
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| Lu Y |
|
Lu |
Yi |
Y |
|
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| Lucae S |
|
Lucae |
Susanne |
S |
|
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| Marmar C |
|
Marmar |
Charles |
C |
|
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| Martin NG |
|
Martin |
Nicholas G |
NG |
|
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| Mayoral F |
|
Mayoral |
Fermin |
F |
|
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| McIntosh AM |
|
McIntosh |
Andrew M |
AM |
|
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| McLaughlin KA |
|
McLaughlin |
Katie A |
KA |
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| McLean SA |
|
McLean |
Samuel A |
SA |
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| McQuillin A |
|
McQuillin |
Andrew |
A |
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| Medland SE |
|
Medland |
Sarah E |
SE |
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| Meyer-Lindenberg A |
|
Meyer-Lindenberg |
Andreas |
A |
|
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| Milanova V |
|
Milanova |
Vihra |
V |
|
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| Mitchell PB |
|
Mitchell |
Philip B |
PB |
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| Molina E |
|
Molina |
Esther |
E |
|
|
| Mowry B |
|
Mowry |
Bryan |
B |
|
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| Muller-Myhsok B |
|
Muller-Myhsok |
Bertram |
B |
|
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| Mullins N |
|
Mullins |
Niamh |
N |
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| Murray R |
|
Murray |
Robin |
R |
|
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| Nöthen MM |
|
Nöthen |
Markus M |
MM |
|
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| Nurnberger JI |
|
Nurnberger |
John I |
JI |
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| O'Connell KS |
|
O'Connell |
Kevin S |
KS |
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| Ophoff RA |
|
Ophoff |
Roel A |
RA |
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| Orcutt HK |
|
Orcutt |
Holly K |
HK |
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| Owen MJ |
|
Owen |
Michael J |
MJ |
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| Palotie A |
|
Palotie |
Aarno |
A |
|
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| Pato C |
|
Pato |
Carlos |
C |
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| Pato M |
|
Pato |
Michele |
M |
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| Pawlak J |
|
Pawlak |
Joanna |
J |
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| Peters T |
|
Peters |
Triinu |
T |
|
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| Petryshen TL |
|
Petryshen |
Tracey L |
TL |
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| Pistis G |
|
Pistis |
Giorgio |
G |
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|
Potash |
James B |
JB |
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|
Powell |
John |
J |
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|
Preisig |
Martin |
M |
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| Quested D |
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Quested |
Digby |
D |
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| Ramos-Quiroga JA |
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Ramos-Quiroga |
Josep A |
JA |
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| Reif A |
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Reif |
Andreas |
A |
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| Ressler KJ |
|
Ressler |
Kerry J |
KJ |
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| Ribasés M |
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Ribasés |
Marta |
M |
|
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| Rietschel M |
|
Rietschel |
Marcella |
M |
|
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| Risbrough VB |
|
Risbrough |
Victoria B |
VB |
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| Rivera M |
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Rivera |
Margarita |
M |
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| Rothbaum AO |
|
Rothbaum |
Alex O |
AO |
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| Rothbaum BO |
|
Rothbaum |
Barbara O |
BO |
|
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| Rujescu D |
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Rujescu |
Dan |
D |
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| Saito T |
|
Saito |
Takeo |
T |
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| Sanders AR |
|
Sanders |
Alan R |
AR |
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| Schachar RJ |
|
Schachar |
Russell J |
RJ |
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| Schofield PR |
|
Schofield |
Peter R |
PR |
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| Schulte EC |
|
Schulte |
Eva C |
EC |
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| Schulze TG |
|
Schulze |
Thomas G |
TG |
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| Scott LJ |
|
Scott |
Laura J |
LJ |
|
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| Seedat S |
|
Seedat |
Soraya |
S |
|
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| Sheerin C |
|
Sheerin |
Christina |
C |
|
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| Shi J |
|
Shi |
Jianxin |
J |
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| Sklar P |
|
Sklar |
Pamela |
P |
|
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| Smalley S |
|
Smalley |
Susan |
S |
|
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| Smeland OB |
|
Smeland |
Olav B |
OB |
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| Smoller JW |
|
Smoller |
Jordan W |
JW |
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| Sonuga-Barke E |
|
Sonuga-Barke |
Edmund |
E |
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| Clair DS |
|
Clair |
David St |
DS |
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| Steen NE |
|
Steen |
Nils Eiel |
NE |
|
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| Stein D |
|
Stein |
Dan |
D |
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| Stein F |
|
Stein |
Frederike |
F |
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| Stein MB |
|
Stein |
Murray B |
MB |
|
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| Streit F |
|
Streit |
Fabian |
F |
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| Swerdlow N |
|
Swerdlow |
Neal |
N |
|
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| Thibaut F |
|
Thibaut |
Florence |
F |
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| Thygesen JH |
|
Thygesen |
Johan H |
JH |
|
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| Timerbulatov I |
|
Timerbulatov |
Ilgiz |
I |
|
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| Toma C |
|
Toma |
Claudio |
C |
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| Trapido E |
|
Trapido |
Edward |
E |
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| Tremblay M |
|
Tremblay |
Micheline |
M |
|
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| Tsuang MT |
|
Tsuang |
Ming T |
MT |
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| Uddin M |
|
Uddin |
Monica |
M |
|
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| Vawter MP |
|
Vawter |
Marquis P |
MP |
|
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| Vincent JB |
|
Vincent |
John B |
JB |
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| Völzke H |
|
Völzke |
Henry |
H |
|
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| Walters JT |
|
Walters |
James T |
JT |
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| Weickert CS |
|
Weickert |
Cynthia S |
CS |
|
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| Weiss LA |
|
Weiss |
Lauren A |
LA |
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| Weissman MM |
|
Weissman |
Myrna M |
MM |
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| Werge T |
|
Werge |
Thomas |
T |
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| Witt SH |
|
Witt |
Stephanie H |
SH |
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| Xavier M |
|
Xavier |
Miguel |
M |
|
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| Yolken R |
|
Yolken |
Robert |
R |
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| Young RM |
|
Young |
Ross M |
RM |
|
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| Zayats T |
|
Zayats |
Tetyana |
T |
|
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| Zoellner LA |
|
Zoellner |
Lori A |
LA |
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|
AGP Consortium |
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|
PEIC Psychosis Endophenotypes International Consortium |
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ADHD Working Group of the Psychiatric Genomics Consortium |
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Autism Working Group of the Psychiatric Genomics Consortium |
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Bipolar Disorder Working Group of the Psychiatric Genomics Consortium |
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Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium |
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PTSD Working Group of the Psychiatric Genomics Consortium |
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Schizophrenia Working Group of the Psychiatric Genomics Consortium |
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CNV Working Group of the Psychiatric Genomics Consortium |
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| Kendall K |
|
Kendall |
Kimberley |
K |
|
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| Riley B |
|
Riley |
Brien |
B |
|
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| Wray NR |
|
Wray |
Naomi R |
NR |
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| O'Donovan MC |
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O'Donovan |
Michael C |
MC |
|
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| Sullivan PF |
|
Sullivan |
Patrick F |
PF |
|
|
| Sanchez-Roige S |
|
Sanchez-Roige |
Sandra |
S |
|
|
| Nievergelt CM |
|
Nievergelt |
Caroline M |
CM |
|
|
| Jacquemont S |
|
Jacquemont |
Sébastien |
S |
|
|
| Scherer SW |
|
Scherer |
Stephen W |
SW |
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| Sebat J |
|
Sebat |
Jonathan |
J |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: medRxiv : the preprint server for health sciences |
| ISOABBREVIATION: medRxiv |
| YEAR: 2025 |
| MONTH: Jul |
| DAY: 16 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: |
| ISSNTYPE: |
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| MEDLINE JOURNAL |
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| MEDLINETA: medRxiv |
| COUNTRY: United States |
| ISSNLINKING: |
| NLMUNIQUEID: 101767986 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Preprint |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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