Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30930738
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
2019
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
U01 AG032984 NIA NIH HHS United States
U01 AG016976 NIA NIH HHS United States
R01 EB000790 NIBIB 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
Wellcome Trust United Kingdom
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