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PMID |
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TITLE |
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder. |
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ABSTRACT |
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Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree ( ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2018/02/06 |
accepted |
2018/08/06 |
entrez |
2018/10/16 06:00 |
pubmed |
2018/10/16 06:00 |
medline |
2018/10/16 06:01 |
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AUTHORS |
|
NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
de Jong S |
|
de Jong |
Simone |
S |
|
National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK. |
Diniz MJA |
|
Diniz |
Mateus Jose Abdalla |
MJA |
|
Pax Instituto de Psiquiatria, BR153, km 505, Villa Sul V, Aparecida de Goiânia, 74911-516, Brazil. |
Saloma A |
|
Saloma |
Andiara |
A |
|
Pax Instituto de Psiquiatria, BR153, km 505, Villa Sul V, Aparecida de Goiânia, 74911-516, Brazil. |
Gadelha A |
|
Gadelha |
Ary |
A |
|
Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001, Brazil. |
Santoro ML |
|
Santoro |
Marcos L |
ML |
|
Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001, Brazil. |
Ota VK |
|
Ota |
Vanessa K |
VK |
|
Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001, Brazil. |
Noto C |
|
Noto |
Cristiano |
C |
|
Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001, Brazil. |
|
Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium |
|
|
|
|
|
Curtis C |
|
Curtis |
Charles |
C |
|
National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK. |
Newhouse SJ |
|
Newhouse |
Stephen J |
SJ |
|
Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, NW1 2DA, UK. |
Patel H |
|
Patel |
Hamel |
H |
|
Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK. |
Hall LS |
|
Hall |
Lynsey S |
LS |
|
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, CF10 3AT, UK. |
O Reilly PF |
|
O Reilly |
Paul F |
PF |
|
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, SE5 8AF, UK. |
Belangero SI |
|
Belangero |
Sintia I |
SI |
|
Department of Morphology and Genetics, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001, Brazil. |
Bressan RA |
|
Bressan |
Rodrigo A |
RA |
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Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, 04021-001, Brazil. |
Breen G |
|
Breen |
Gerome |
G |
|
National Institute of Health Research Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK. gerome.breen@gmail.com. |
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INVESTIGATORS |
|
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
Wray |
Naomi R |
NR |
|
Ripke |
Stephan |
S |
|
Mattheisen |
Manuel |
M |
|
Trzaskowski |
Maciej |
M |
|
Byrne |
Enda M |
EM |
|
Abdellaoui |
Abdel |
A |
|
Adams |
Mark J |
MJ |
|
Agerbo |
Esben |
E |
|
Air |
Tracy M |
TM |
|
Andlauer |
Till F M |
TFM |
|
Bacanu |
Silviu-Alin |
SA |
|
Bækvad-Hansen |
Marie |
M |
|
Beekman |
Aartjan T F |
ATF |
|
Bigdeli |
Tim B |
TB |
|
Binder |
Elisabeth B |
EB |
|
Blackwood |
Douglas H R |
DHR |
|
Bryois |
Julien |
J |
|
Buttenschøn |
Henriette N |
HN |
|
Bybjerg-Grauholm |
Jonas |
J |
|
Cai |
Na |
N |
|
Castelao |
Enrique |
E |
|
Christensen |
Jane Hvarregaard |
JH |
|
Clarke |
Toni-Kim |
TK |
|
Coleman |
Jonathan R I |
JRI |
|
Colodro-Conde |
Lucía |
L |
|
Couvy-Duchesne |
Baptiste |
B |
|
Craddock |
Nick |
N |
|
Crawford |
Gregory E |
GE |
|
Davies |
Gail |
G |
|
Deary |
Ian J |
IJ |
|
Degenhardt |
Franziska |
F |
|
Derks |
Eske M |
EM |
|
Direk |
Nese |
N |
|
Dolan |
Conor V |
CV |
|
Dunn |
Erin C |
EC |
|
Eley |
Thalia C |
TC |
|
Escott-Price |
Valentina |
V |
|
Kiadeh |
Farnush Farhadi Hassan |
FFH |
|
Finucane |
Hilary K |
HK |
|
Forstner |
Andreas J |
AJ |
|
Frank |
Josef |
J |
|
Gaspar |
Héléna A |
HA |
|
Gill |
Michael |
M |
|
Goes |
Fernando S |
FS |
|
Gordon |
Scott D |
SD |
|
Grove |
Jakob |
J |
|
Hansen |
Christine Søholm |
CS |
|
Hansen |
Thomas F |
TF |
|
Herms |
Stefan |
S |
|
Hickie |
Ian B |
IB |
|
Hoffmann |
Per |
P |
|
Homuth |
Georg |
G |
|
Horn |
Carsten |
C |
|
Hottenga |
Jouke-Jan |
JJ |
|
Hougaard |
David M |
DM |
|
Ising |
Marcus |
M |
|
Jansen |
Rick |
R |
|
Jones |
Ian |
I |
|
Jones |
Lisa A |
LA |
|
Jorgenson |
Eric |
E |
|
Knowles |
James A |
JA |
|
Kohane |
Isaac S |
IS |
|
Kraft |
Julia |
J |
|
Kretzschmar |
Warren W |
WW |
|
Krogh |
Jesper |
J |
|
Kutalik |
Zoltán |
Z |
|
Li |
Yihan |
Y |
|
Lind |
Penelope A |
PA |
|
MacIntyre |
Donald J |
DJ |
|
MacKinnon |
Dean F |
DF |
|
Maier |
Robert M |
RM |
|
Maier |
Wolfgang |
W |
|
Marchini |
Jonathan |
J |
|
Mbarek |
Hamdi |
H |
|
McGrath |
Patrick |
P |
|
McGuffin |
Peter |
P |
|
Medland |
Sarah E |
SE |
|
Mehta |
Divya |
D |
|
Middeldorp |
Christel M |
CM |
|
Mihailov |
Evelin |
E |
|
Milaneschi |
Yuri |
Y |
|
Milani |
Lili |
L |
|
Mondimore |
Francis M |
FM |
|
Montgomery |
Grant W |
GW |
|
Mostafavi |
Sara |
S |
|
Mullins |
Niamh |
N |
|
Nauck |
Matthias |
M |
|
Ng |
Bernard |
B |
|
Nivard |
Michel G |
MG |
|
Nyholt |
Dale R |
DR |
|
Oskarsson |
Hogni |
H |
|
Owen |
Michael J |
MJ |
|
Painter |
Jodie N |
JN |
|
Pedersen |
Carsten Bøcker |
CB |
|
Pedersen |
Marianne Giørtz |
MG |
|
Peterson |
Roseann E |
RE |
|
Pettersson |
Erik |
E |
|
Peyrot |
Wouter J |
WJ |
|
Pistis |
Giorgio |
G |
|
Posthuma |
Danielle |
D |
|
Quiroz |
Jorge A |
JA |
|
Qvist |
Per |
P |
|
Rice |
John P |
JP |
|
Riley |
Brien P |
BP |
|
Rivera |
Margarita |
M |
|
Mirza |
Saira Saeed |
SS |
|
Schoevers |
Robert |
R |
|
Schulte |
Eva C |
EC |
|
Shen |
Ling |
L |
|
Shyn |
Stanley I |
SI |
|
Sigurdsson |
Engilbert |
E |
|
Sinnamon |
Grant C B |
GCB |
|
Smit |
Johannes H |
JH |
|
Smith |
Daniel J |
DJ |
|
Stefansson |
Hreinn |
H |
|
Steinberg |
Stacy |
S |
|
Streit |
Fabian |
F |
|
Strohmaier |
Jana |
J |
|
Tansey |
Katherine E |
KE |
|
Teismann |
Henning |
H |
|
Teumer |
Alexander |
A |
|
Thompson |
Wesley |
W |
|
Thomson |
Pippa A |
PA |
|
Thorgeirsson |
Thorgeir E |
TE |
|
Traylor |
Matthew |
M |
|
Treutlein |
Jens |
J |
|
Trubetskoy |
Vassily |
V |
|
Uitterlinden |
André G |
AG |
|
Umbricht |
Daniel |
D |
|
Van der Auwera |
Sandra |
S |
|
van Hemert |
Albert M |
AM |
|
Viktorin |
Alexander |
A |
|
Visscher |
Peter M |
PM |
|
Wang |
Yunpeng |
Y |
|
Webb |
Bradley T |
BT |
|
Weinsheimer |
Shantel Marie |
SM |
|
Wellmann |
Jürgen |
J |
|
Willemsen |
Gonneke |
G |
|
Witt |
Stephanie H |
SH |
|
Wu |
Yang |
Y |
|
Xi |
Hualin S |
HS |
|
Yang |
Jian |
J |
|
Zhang |
Futao |
F |
|
Arolt |
Volker |
V |
|
Baune |
Bernhard T |
BT |
|
Berger |
Klaus |
K |
|
Boomsma |
Dorret I |
DI |
|
Cichon |
Sven |
S |
|
Dannlowski |
Udo |
U |
|
de Geus |
E J C |
EJC |
|
DePaulo |
J Raymond |
JR |
|
Domenici |
Enrico |
E |
|
Domschke |
Katharina |
K |
|
Esko |
Tõnu |
T |
|
Grabe |
Hans J |
HJ |
|
Hamilton |
Steven P |
SP |
|
Hayward |
Caroline |
C |
|
Heath |
Andrew C |
AC |
|
Kendler |
Kenneth S |
KS |
|
Kloiber |
Stefan |
S |
|
Lewis |
Glyn |
G |
|
Li |
Qingqin S |
QS |
|
Lucae |
Susanne |
S |
|
Madden |
Pamela A F |
PAF |
|
Magnusson |
Patrik K |
PK |
|
Martin |
Nicholas G |
NG |
|
McIntosh |
Andrew M |
AM |
|
Metspalu |
Andres |
A |
|
Mors |
Ole |
O |
|
Mortensen |
Preben Bo |
PB |
|
Müller-Myhsok |
Bertram |
B |
|
Nordentoft |
Merete |
M |
|
Nöthen |
Markus M |
MM |
|
O'Donovan |
Michael C |
MC |
|
Paciga |
Sara A |
SA |
|
Pedersen |
Nancy L |
NL |
|
Penninx |
Brenda W J H |
BWJH |
|
Perlis |
Roy H |
RH |
|
Porteous |
David J |
DJ |
|
Potash |
James B |
JB |
|
Preisig |
Martin |
M |
|
Rietschel |
Marcella |
M |
|
Schaefer |
Catherine |
C |
|
Schulze |
Thomas G |
TG |
|
Smoller |
Jordan W |
JW |
|
Stefansson |
Kari |
K |
|
Tiemeier |
Henning |
H |
|
Uher |
Rudolf |
R |
|
Völzke |
Henry |
H |
|
Weissman |
Myrna M |
MM |
|
Werge |
Thomas |
T |
|
Lewis |
Cathryn M |
CM |
|
Levinson |
Douglas F |
DF |
|
Børglum |
Anders D |
AD |
|
Sullivan |
Patrick F |
PF |
|
Meier |
Sandra |
S |
|
Strauss |
John |
J |
|
Xu |
Wei |
W |
|
Vincent |
John B |
JB |
|
Matthews |
Keith |
K |
|
Ferreira |
Manuel |
M |
|
O'Dushlaine |
Colm |
C |
|
Purcell |
Shaun |
S |
|
Raychaudhuri |
Soumya |
S |
|
Ruderfer |
Douglas M |
DM |
|
Sklar |
Pamela |
P |
|
Scott |
Laura J |
LJ |
|
Flickinger |
Matthew |
M |
|
Burmeister |
Margit |
M |
|
Li |
Jun |
J |
|
Guan |
Weihua |
W |
|
Absher |
Devin |
D |
|
Thompson |
Robert C |
RC |
|
Meng |
Fan Guo |
FG |
|
Schatzberg |
Alan F |
AF |
|
Bunney |
William E |
WE |
|
Barchas |
Jack D |
JD |
|
Watson |
Stanley J |
SJ |
|
Myers |
Richard M |
RM |
|
Akil |
Huda |
H |
|
Boehnke |
Michael |
M |
|
Chambert |
Kimberly |
K |
|
Moran |
Jennifer |
J |
|
Scolnick |
Edward |
E |
|
Djurovic |
Srdjan |
S |
|
Melle |
Ingrid |
I |
|
Morken |
Gunnar |
G |
|
Corvin |
Aiden |
A |
|
Anjorin |
Adebayo |
A |
|
Kandaswamy |
Radhika |
R |
|
Lawrence |
Jacob |
J |
|
McLean |
Alan W |
AW |
|
Pickard |
Benjamin S |
BS |
|
Bergen |
Sarah E |
SE |
|
Nimgaonkar |
Vishwajit |
V |
|
Landén |
Mikael |
M |
|
Schalling |
Martin |
M |
|
Osby |
Urban |
U |
|
Backlund |
Lena |
L |
|
Frisén |
Louise |
L |
|
Langstrom |
Niklas |
N |
|
Stahl |
Eli |
E |
|
Dobbyn |
Amanda |
A |
|
Jamain |
Stéphane |
S |
|
Etain |
Bruno |
B |
|
Bellivier |
Frank |
F |
|
Leber |
Markus |
M |
|
Maaser |
Anna |
A |
|
Fischer |
Sascha B |
SB |
|
Reinbold |
Céline S |
CS |
|
Kittel-Schneider |
Sarah |
S |
|
Fullerton |
Janice M |
JM |
|
Oruč |
Lilijana |
L |
|
Para |
José G |
JG |
|
Mayoral |
Fermin |
F |
|
Rivas |
Fabio |
F |
|
Czerski |
Piotr M |
PM |
|
Kammerer-Ciernioch |
Jutta |
J |
|
Vedder |
Helmut |
H |
|
Borrmann-Hassenbach |
Margitta |
M |
|
Pfennig |
Andrea |
A |
|
Brennan |
Paul |
P |
|
McKay |
James D |
JD |
|
Kogevinas |
Manolis |
M |
|
Schwarz |
Markus |
M |
|
Schofield |
Peter R |
PR |
|
Mühleisen |
Thomas W |
TW |
|
Schumacher |
Johannes |
J |
|
Bauer |
Michael |
M |
|
Wright |
Adam |
A |
|
Mitchell |
Philip B |
PB |
|
Hautzinger |
Martin |
M |
|
Kelsoe |
John R |
JR |
|
Greenwood |
Tiffany A |
TA |
|
Nievergelt |
Caroline M |
CM |
|
Shilling |
Paul D |
PD |
|
Smith |
Erin N |
EN |
|
Bloss |
Cinnamon S |
CS |
|
Edenberg |
Howard J |
HJ |
|
Koller |
Daniel L |
DL |
|
Gershon |
Elliot S |
ES |
|
Liu |
Chunyu |
C |
|
Badner |
Judith A |
JA |
|
Scheftner |
William A |
WA |
|
Lawson |
William B |
WB |
|
Nwulia |
Evaristus A |
EA |
|
Hipolito |
Maria |
M |
|
Coryell |
William |
W |
|
Rice |
John |
J |
|
Byerley |
William |
W |
|
McMahon |
Francis J |
FJ |
|
Lohoff |
Falk W |
FW |
|
Zandi |
Peter P |
PP |
|
Mahon |
Pamela B |
PB |
|
McInnis |
Melvin G |
MG |
|
Zöllner |
Sebastian |
S |
|
Zhang |
Peng |
P |
|
Szelinger |
Szabolcs |
S |
|
St Clair |
David |
D |
|
Caesar |
Sian |
S |
|
Gordon-Smith |
Katherine |
K |
|
Fraser |
Christine |
C |
|
Green |
Elaine K |
EK |
|
Grozeva |
Detelina |
D |
|
Hamshere |
Marian L |
ML |
|
Kirov |
George |
G |
|
Nikolov |
Ivan |
I |
|
Collier |
David A |
DA |
|
Elkin |
Amanda |
A |
|
Williamson |
Richard |
R |
|
Young |
Allan H |
AH |
|
Ferrier |
I Nicol |
IN |
|
Milanova |
Vihra |
V |
|
Alda |
Martin |
M |
|
Cervantes |
Pablo |
P |
|
Cruceanu |
Cristiana |
C |
|
Rouleau |
Guy A |
GA |
|
Turecki |
Gustavo |
G |
|
Paciga |
Sara |
S |
|
Winslow |
Ashley R |
AR |
|
Grigoroiu-Serbanescu |
Maria |
M |
|
Ophoff |
Roel |
R |
|
Adolfsson |
Rolf |
R |
|
Adolfsson |
Annelie Nordin |
AN |
|
Del-Favero |
Jurgen |
J |
|
Pato |
Carlos |
C |
|
Biernacka |
Joanna M |
JM |
|
Frye |
Mark A |
MA |
|
Morris |
Derek |
D |
|
Schork |
Nicholas J |
NJ |
|
Reif |
Andreas |
A |
|
Lissowska |
Jolanta |
J |
|
Hauser |
Joanna |
J |
|
Szeszenia-Dabrowska |
Neonila |
N |
|
McGhee |
Kevin |
K |
|
Quinn |
Emma |
E |
|
Moskvina |
Valentina |
V |
|
Holmans |
Peter A |
PA |
|
Farmer |
Anne |
A |
|
Kennedy |
James L |
JL |
|
Andreassen |
Ole A |
OA |
|
Mattingsdal |
Morten |
M |
|
Gill |
Michael |
M |
|
Bass |
Nicholas J |
NJ |
|
Gurling |
Hugh |
H |
|
McQuillin |
Andrew |
A |
|
Breuer |
René |
R |
|
Hultman |
Christina |
C |
|
Lichtenstein |
Paul |
P |
|
Huckins |
Laura M |
LM |
|
Leboyer |
Marion |
M |
|
Lathrop |
Mark |
M |
|
Nurnberger |
John |
J |
|
Steffens |
Michael |
M |
|
Foroud |
Tatiana M |
TM |
|
Berrettini |
Wade H |
WH |
|
Craig |
David W |
DW |
|
Shi |
Jianxin |
J |
|
|
JOURNAL |
|
VOLUME: 1 |
ISSUE: |
TITLE: Communications biology |
ISOABBREVIATION: Commun Biol |
YEAR: 2018 |
MONTH: |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 2399-3642 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Commun Biol |
COUNTRY: England |
ISSNLINKING: 2399-3642 |
NLMUNIQUEID: 101719179 |
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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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NOTE |
Cites |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
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Wellcome Trust |
United Kingdom |
G0200243 |
Medical Research Council |
United Kingdom |
G0401207 |
Medical Research Council |
United Kingdom |
U01 MH109536 |
NIMH NIH HHS |
United States |
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