|
|
| PMID |
|
|
| TITLE |
|
| Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. |
|
| ABSTRACT |
|
|
|
| Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the and genes could explain parts of the shared and distinct features of AD and BIP. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2018/01/30 |
| accepted |
2019/02/26 |
| entrez |
2019/04/02 06:00 |
| pubmed |
2019/04/02 06:00 |
| medline |
2019/04/02 06:01 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Drange OK |
|
Drange |
Ole Kristian |
OK |
|
Department of Østmarka, Division of Mental Health Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. |
| Smeland OB |
|
Smeland |
Olav Bjerkehagen |
OB |
|
Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. |
| Shadrin AA |
|
Shadrin |
Alexey A |
AA |
|
Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. |
| Finseth PI |
|
Finseth |
Per Ivar |
PI |
|
Department of Brøset, Division of Mental Health Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. |
| Witoelar A |
|
Witoelar |
Aree |
A |
|
Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. |
| Frei O |
|
Frei |
Oleksandr |
O |
|
Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. |
|
Psychiatric Genomics Consortium Bipolar Disorder Working Group |
|
|
|
|
|
| Wang Y |
|
Wang |
Yunpeng |
Y |
|
Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. |
| Hassani S |
|
Hassani |
Sahar |
S |
|
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. |
| Djurovic S |
|
Djurovic |
Srdjan |
S |
|
Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway. |
| Dale AM |
|
Dale |
Anders M |
AM |
|
Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States. |
| Andreassen OA |
|
Andreassen |
Ole A |
OA |
|
Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Stahl |
Eli A |
EA |
|
| Breen |
Gerome |
G |
|
| Forstner |
Andreas J |
AJ |
|
| McQuillin |
Andrew |
A |
|
| Ripke |
Stephan |
S |
|
| Trubetskoy |
Vassily |
V |
|
| Mattheisen |
Manuel |
M |
|
| Wang |
Yunpeng |
Y |
|
| Coleman |
Jonathan R I |
JRI |
|
| Gaspar |
Heìleìna A |
HA |
|
| de Leeuw |
Christiaan A |
CA |
|
| Steinberg |
Stacy |
S |
|
| Pavlides |
Jennifer M Whitehead |
JMW |
|
| Trzaskowski |
Maciej |
M |
|
| Pers |
Tune H |
TH |
|
| Holmans |
Peter A |
PA |
|
| Abbott |
Liam |
L |
|
| Agerbo |
Esben |
E |
|
| Akil |
Huda |
H |
|
| Albani |
Diego |
D |
|
| Alliey-Rodriguez |
Ney |
N |
|
| Als |
Thomas D |
TD |
|
| Anjorin |
Adebayo |
A |
|
| Antilla |
Verneri |
V |
|
| Awasthi |
Swapnil |
S |
|
| Badner |
Judith A |
JA |
|
| Bækvad-Hansen |
Marie |
M |
|
| Barchas |
Jack D |
JD |
|
| Bass |
Nicholas |
N |
|
| Bauer |
Michael |
M |
|
| Belliveau |
Richard |
R |
|
| Bergen |
Sarah E |
SE |
|
| Pedersen |
Carsten Bøcker |
CB |
|
| Bøen |
Erlend |
E |
|
| Boks |
Marco |
M |
|
| Boocock |
James |
J |
|
| Budde |
Monika |
M |
|
| Bunney |
William |
W |
|
| Burmeister |
Margit |
M |
|
| Bybjerg-Grauholm |
Jonas |
J |
|
| Byerley |
William |
W |
|
| Casas |
Miquel |
M |
|
| Cerrato |
Felecia |
F |
|
| Cervantes |
Pablo |
P |
|
| Chambert |
Kimberly |
K |
|
| Charney |
Alexander W |
AW |
|
| Chen |
Danfeng |
D |
|
| Churchhouse |
Claire |
C |
|
| Clarke |
Toni-Kim |
TK |
|
| Coryell |
William |
W |
|
| Craig |
David W |
DW |
|
| Cruceanu |
Cristiana |
C |
|
| Curtis |
David |
D |
|
| Czerski |
Piotr M |
PM |
|
| Dale |
Anders M |
AM |
|
| de Jong |
Simone |
S |
|
| Degenhardt |
Franziska |
F |
|
| Del-Favero |
Jurgen |
J |
|
| DePaulo |
J Raymond |
JR |
|
| Djurovic |
Srdjan |
S |
|
| Dobbyn |
Amanda L |
AL |
|
| Dumont |
Ashley |
A |
|
| Elvsåshagen |
Torbjørn |
T |
|
| Escott-Price |
Valentina |
V |
|
| Fan |
Chun Chieh |
CC |
|
| Fischer |
Sascha B |
SB |
|
| Flickinger |
Matthew |
M |
|
| Foroud |
Tatiana M |
TM |
|
| Forty |
Liz |
L |
|
| Frank |
Josef |
J |
|
| Fraser |
Christine |
C |
|
| Freimer |
Nelson B |
NB |
|
| Friseìn |
Louise |
L |
|
| Gade |
Katrin |
K |
|
| Gage |
Diane |
D |
|
| Garnham |
Julie |
J |
|
| Giambartolomei |
Claudia |
C |
|
| Pedersen |
Marianne Giørtz |
MG |
|
| Goldstein |
Jaqueline |
J |
|
| Gordon |
Scott D |
SD |
|
| Gordon-Smith |
Katherine |
K |
|
| Green |
Elaine K |
EK |
|
| Green |
Melissa J |
MJ |
|
| Greenwood |
Tiffany A |
TA |
|
| Grove |
Jakob |
J |
|
| Guan |
Weihua |
W |
|
| Parra |
Joseì Guzman |
JG |
|
| Hamshere |
Marian L |
ML |
|
| Hautzinger |
Martin |
M |
|
| Heilbronner |
Urs |
U |
|
| Herms |
Stefan |
S |
|
| Hipolito |
Maria |
M |
|
| Hoffmann |
Per |
P |
|
| Holland |
Dominic |
D |
|
| Huckins |
Laura |
L |
|
| Jamain |
Steìphane |
S |
|
| Johnson |
Jessica S |
JS |
|
| Jureìus |
Anders |
A |
|
| Kandaswamy |
Radhika |
R |
|
| Karlsson |
Robert |
R |
|
| Kennedy |
James L |
JL |
|
| Kittel-Schneider |
Sarah |
S |
|
| Knott |
Sarah V |
SV |
|
| Knowles |
James A |
JA |
|
| Kogevinas |
Manolis |
M |
|
| Koller |
Anna C |
AC |
|
| Kupka |
Ralph |
R |
|
| Lavebratt |
Catharina |
C |
|
| Lawrence |
Jacob |
J |
|
| Lawson |
William B |
WB |
|
| Leber |
Markus |
M |
|
| Lee |
Phil H |
PH |
|
| Levy |
Shawn E |
SE |
|
| Li |
Jun Z |
JZ |
|
| Liu |
Chunyu |
C |
|
| Lucae |
Susanne |
S |
|
| Maaser |
Anna |
A |
|
| MacIntyre |
Donald J |
DJ |
|
| Mahon |
Pamela B |
PB |
|
| Maier |
Wolfgang |
W |
|
| Martinsson |
Lina |
L |
|
| McCarroll |
Steve |
S |
|
| McGuffin |
Peter |
P |
|
| McInnis |
Melvin G |
MG |
|
| McKay |
James D |
JD |
|
| Medeiros |
Helena |
H |
|
| Medland |
Sarah E |
SE |
|
| Meng |
Fan |
F |
|
| Milani |
Lili |
L |
|
| Montgomery |
Grant W |
GW |
|
| Morris |
Derek W |
DW |
|
| Mühleisen |
Thomas W |
TW |
|
| Mullins |
Niamh |
N |
|
| Nguyen |
Hoang |
H |
|
| Nievergelt |
Caroline M |
CM |
|
| Adolfsson |
Annelie Nordin |
AN |
|
| Nwulia |
Evaristus A |
EA |
|
| O'Donovan |
Claire |
C |
|
| Loohuis |
Loes M Olde |
LMO |
|
| Ori |
Anil P S |
APS |
|
| Oruc |
Lilijana |
L |
|
| Ösby |
Urban |
U |
|
| Perlis |
Roy H |
RH |
|
| Perry |
Amy |
A |
|
| Pfennig |
Andrea |
A |
|
| Potash |
James B |
JB |
|
| Purcell |
Shaun M |
SM |
|
| Regeer |
Eline J |
EJ |
|
| Reif |
Andreas |
A |
|
| Reinbold |
Ceìline S |
CS |
|
| Rice |
John P |
JP |
|
| Rivas |
Fabio |
F |
|
| Rivera |
Margarita |
M |
|
| Roussos |
Panos |
P |
|
| Ruderfer |
Douglas M |
DM |
|
| Ryu |
Euijung |
E |
|
| Saìnchez-Mora |
Cristina |
C |
|
| Schatzberg |
Alan F |
AF |
|
| Scheftner |
William A |
WA |
|
| Schork |
Nicholas J |
NJ |
|
| Weickert |
Cynthia Shannon |
CS |
|
| Shehktman |
Tatyana |
T |
|
| Shilling |
Paul D |
PD |
|
| Sigurdsson |
Engilbert |
E |
|
| Slaney |
Claire |
C |
|
| Smeland |
Olav B |
OB |
|
| Sobell |
Janet L |
JL |
|
| Hansen |
Christine Søholm |
CS |
|
| Spijker |
Anne T |
AT |
|
| Clair |
David St |
DS |
|
| Steffens |
Michael |
M |
|
| Strauss |
John S |
JS |
|
| Streit |
Fabian |
F |
|
| Strohmaier |
Jana |
J |
|
| Szelinger |
Szabolcs |
S |
|
| Thompson |
Robert C |
RC |
|
| Thorgeirsson |
Thorgeir E |
TE |
|
| Treutlein |
Jens |
J |
|
| Vedder |
Helmut |
H |
|
| Wang |
Weiqing |
W |
|
| Watson |
Stanley J |
SJ |
|
| Weickert |
Thomas W |
TW |
|
| Witt |
Stephanie H |
SH |
|
| Xi |
Simon |
S |
|
| Xu |
Wei |
W |
|
| Young |
Allan H |
AH |
|
| Zandi |
Peter |
P |
|
| Zhang |
Peng |
P |
|
| Zollner |
Sebastian |
S |
|
| Adolfsson |
Rolf |
R |
|
| Agartz |
Ingrid |
I |
|
| Alda |
Martin |
M |
|
| Backlund |
Lena |
L |
|
| Baune |
Bernhard T |
BT |
|
| Bellivier |
Frank |
F |
|
| Berrettini |
Wade H |
WH |
|
| Biernacka |
Joanna M |
JM |
|
| Blackwood |
Douglas H R |
DHR |
|
| Boehnke |
Michael |
M |
|
| Børglum |
Anders D |
AD |
|
| Corvin |
Aiden |
A |
|
| Craddock |
Nicholas |
N |
|
| Daly |
Mark J |
MJ |
|
| Dannlowski |
Udo |
U |
|
| Esko |
ToÞnu |
T |
|
| Etain |
Bruno |
B |
|
| Frye |
Mark |
M |
|
| Fullerton |
Janice M |
JM |
|
| Gershon |
Elliot S |
ES |
|
| Gill |
Michael |
M |
|
| Goes |
Fernando |
F |
|
| Grigoroiu-Serbanescu |
Maria |
M |
|
| Hauser |
Joanna |
J |
|
| Hougaard |
David M |
DM |
|
| Hultman |
Christina M |
CM |
|
| Jones |
Ian |
I |
|
| Jones |
Lisa A |
LA |
|
| Kahn |
Reneì S |
RS |
|
| Kirov |
George |
G |
|
| Landeìn |
Mikael |
M |
|
| Leboyer |
Marion |
M |
|
| Lewis |
Cathryn M |
CM |
|
| Li |
Qingqin S |
QS |
|
| Lissowska |
Jolanta |
J |
|
| Martin |
Nicholas G |
NG |
|
| Mayoral |
Fermin |
F |
|
| McElroy |
Susan L |
SL |
|
| McIntosh |
Andrew M |
AM |
|
| McMahon |
Francis J |
FJ |
|
| Melle |
Ingrid |
I |
|
| Metspalu |
Andres |
A |
|
| Mitchell |
Philip B |
PB |
|
| Morken |
Gunnar |
G |
|
| Mors |
Ole |
O |
|
| Mortensen |
Preben Bo |
PB |
|
| Müller-Myhsok |
Bertram |
B |
|
| Myers |
Richard M |
RM |
|
| Neale |
Benjamin M |
BM |
|
| Nimgaonkar |
Vishwajit |
V |
|
| Nordentoft |
Merete |
M |
|
| Nöthen |
Markus M |
MM |
|
| O'Donovan |
Michael C |
MC |
|
| Oedegaard |
Ketil J |
KJ |
|
| Owen |
Michael J |
MJ |
|
| Paciga |
Sara A |
SA |
|
| Pato |
Carlos |
C |
|
| Pato |
Michele T |
MT |
|
| Posthuma |
Danielle |
D |
|
| Ramos-Quiroga |
Josep Antoni |
JA |
|
| Ribaseìs |
Marta |
M |
|
| Rietschel |
Marcella |
M |
|
| Rouleau |
Guy A |
GA |
|
| Schalling |
Martin |
M |
|
| Schofield |
Peter R |
PR |
|
| Schulze |
Thomas G |
TG |
|
| Serretti |
Alessandro |
A |
|
| Smoller |
Jordan W |
JW |
|
| Stefansson |
Hreinn |
H |
|
| Stefansson |
Kari |
K |
|
| Stordal |
Eystein |
E |
|
| Sullivan |
Patrick F |
PF |
|
| Turecki |
Gustavo |
G |
|
| Vaaler |
Arne E |
AE |
|
| Vieta |
Eduard |
E |
|
| Vincent |
John B |
JB |
|
| Werge |
Thomas |
T |
|
| Nurnberger |
John I |
JI |
|
| Wray |
Naomi R |
NR |
|
| Florio |
Arianna Di |
AD |
|
| Edenberg |
Howard J |
HJ |
|
| Cichon |
Sven |
S |
|
| Ophoff |
Roel A |
RA |
|
| Scott |
Laura J |
LJ |
|
| Andreassen |
Ole A |
OA |
|
| Kelsoe |
John |
J |
|
| Sklar |
Pamela |
P |
|
|
| JOURNAL |
|
| VOLUME: 13 |
| ISSUE: |
| TITLE: Frontiers in neuroscience |
| ISOABBREVIATION: Front Neurosci |
| YEAR: 2019 |
| MONTH: |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Print |
| ISSN: 1662-4548 |
| ISSNTYPE: Print |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Front Neurosci |
| COUNTRY: Switzerland |
| ISSNLINKING: 1662-453X |
| NLMUNIQUEID: 101478481 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| U24 AG021886 |
NIA NIH HHS |
United States |
| G1000708 |
Medical Research Council |
United Kingdom |
| U01 AG032984 |
NIA NIH HHS |
United States |
| R01 NS057198 |
NINDS NIH HHS |
United States |
| R01 HL105756 |
NHLBI NIH HHS |
United States |
| R01 AG033193 |
NIA NIH HHS |
United States |
| U01 MH109536 |
NIMH NIH HHS |
United States |
|
Wellcome Trust |
United Kingdom |
| U01 AG016976 |
NIA NIH HHS |
United States |
| R01 EB000790 |
NIBIB NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
| KEYWORD |
| Alzheimer’s disease |
| GWAS |
| MARK2 |
| VAC14 |
| affective symptoms |
| bipolar disorder |
| cognitive symptoms |
| pleiotropy |
|
| MESH HEADINGS |
|
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
|
|
