Genetic Epidemiology, Psychiatric Genetics, Asthma 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
25640677
TITLE
Joint analysis of psychiatric disorders increases accuracy of risk prediction for schizophrenia, bipolar disorder, and major depressive disorder.
ABSTRACT
Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk.
Copyright 2015 The Authors. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2015 Feb 5
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/10/23
accepted 2014/12/08
aheadofprint 2015/01/29
entrez 2015/02/03 06:00
pubmed 2015/02/03 06:00
medline 2015/04/10 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Maier R Maier Robert R The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Moser G Moser Gerhard G The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Chen GB Chen Guo-Bo GB The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Ripke S Ripke Stephan S Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Cross-Disorder Working Group of the Psychiatric Genomics Consortium
Coryell W Coryell William W Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA.
Potash JB Potash James B JB Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA.
Scheftner WA Scheftner William A WA Department of Psychiatry, Rush University Medical Center, Chicago, IL 60612, USA.
Shi J Shi Jianxin J Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Weissman MM Weissman Myrna M MM Department of Psychiatry, Columbia University, and New York State Psychiatric Institute, New York, NY 10032, USA.
Hultman CM Hultman Christina M CM Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden.
Landén M Landén Mikael M Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the Gothenburg University, 413 45 Gothenburg, Sweden.
Levinson DF Levinson Douglas F DF Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
Kendler KS Kendler Kenneth S KS Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
Smoller JW Smoller Jordan W JW Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Wray NR Wray Naomi R NR The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Lee SH Lee S Hong SH The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: hong.lee@uq.edu.au.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Absher Devin D
Agartz Ingrid I
Akil Huda H
Amin Farooq F
Andreassen Ole A OA
Anjorin Adebayo A
Anney Richard R
Arking Dan E DE
Asherson Philip P
Azevedo Maria H MH
Backlund Lena L
Badner Judith A JA
Bailey Anthony J AJ
Banaschewski Tobias T
Barchas Jack D JD
Barnes Michael R MR
Barrett Thomas B TB
Bass Nicholas N
Battaglia Agatino A
Bauer Michael M
Bayés Mònica M
Bellivier Frank F
Bergen Sarah E SE
Berrettini Wade W
Betancur Catalina C
Bettecken Thomas T
Biederman Joseph J
Binder Elisabeth B EB
Black Donald W DW
Blackwood Douglas H R DH
Bloss Cinnamon S CS
Boehnke Michael M
Boomsma Dorret I DI
Breen Gerome G
Breuer René R
Bruggeman Richard R
Buccola Nancy G NG
Buitelaar Jan K JK
Bunney William E WE
Buxbaum Joseph D JD
Byerley William F WF
Caesar Sian S
Cahn Wiepke W
Cantor Rita M RM
Casas Miguel M
Chakravarti Aravinda A
Chambert Kimberly K
Choudhury Khalid K
Cichon Sven S
Cloninger C Robert CR
Collier David A DA
Cook Edwin H EH
Coon Hilary H
Cormand Bru B
Cormican Paul P
Corvin Aiden A
Coryell William H WH
Craddock Nicholas N
Craig David W DW
Craig Ian W IW
Crosbie Jennifer J
Cuccaro Michael L ML
Curtis David D
Czamara Darina D
Daly Mark J MJ
Datta Susmita S
Dawson Geraldine G
Day Richard R
De Geus Eco J EJ
Degenhardt Franziska F
Devlin Bernie B
Djurovic Srdjan S
Donohoe Gary J GJ
Doyle Alysa E AE
Duan Jubao J
Dudbridge Frank F
Duketis Eftichia E
Ebstein Richard P RP
Edenberg Howard J HJ
Elia Josephine J
Ennis Sean S
Etain Bruno B
Fanous Ayman A
Faraone Stephen V SV
Farmer Anne E AE
Ferrier I Nicol IN
Flickinger Matthew M
Fombonne Eric E
Foroud Tatiana T
Frank Josef J
Franke Barbara B
Fraser Christine C
Freedman Robert R
Freimer Nelson B NB
Freitag Christine M CM
Friedl Marion M
Frisén Louise L
Gallagher Louise L
Gejman Pablo V PV
Georgieva Lyudmila L
Gershon Elliot S ES
Geschwind Daniel H DH
Giegling Ina I
Gill Michael M
Gordon Scott D SD
Gordon-Smith Katherine K
Green Elaine K EK
Greenwood Tiffany A TA
Grice Dorothy E DE
Gross Magdalena M
Grozeva Detelina D
Guan Weihua W
Gurling Hugh H
De Haan Lieuwe L
Haines Jonathan L JL
Hakonarson Hakon H
Hallmayer Joachim J
Hamilton Steven P SP
Hamshere Marian L ML
Hansen Thomas F TF
Hartmann Annette M AM
Hautzinger Martin M
Heath Andrew C AC
Henders Anjali K AK
Herms Stefan S
Hickie Ian B IB
Hipolito Maria M
Hoefels Susanne S
Holmans Peter A PA
Holsboer Florian F
Hoogendijk Witte J WJ
Hottenga Jouke-Jan JJ
Hultman Christina M CM
Hus Vanessa V
Ingason Andrés A
Ising Marcus M
Jamain Stéphane S
Jones Ian I
Jones Lisa L
Kähler Anna K AK
Kahn René S RS
Kandaswamy Radhika R
Keller Matthew C MC
Kelsoe John R JR
Kendler Kenneth S KS
Kennedy James L JL
Kenny Elaine E
Kent Lindsey L
Kim Yunjung Y
Kirov George K GK
Klauck Sabine M SM
Klei Lambertus L
Knowles James A JA
Kohli Martin A MA
Koller Daniel L DL
Konte Bettina B
Korszun Ania A
Krabbendam Lydia L
Krasucki Robert R
Kuntsi Jonna J
Kwan Phoenix P
Landén Mikael M
Långström Niklas N
Lathrop Mark M
Lawrence Jacob J
Lawson William B WB
Leboyer Marion M
Ledbetter David H DH
Lee Phil H PH
Lencz Todd T
Lesch Klaus-Peter KP
Levinson Douglas F DF
Lewis Cathryn M CM
Li Jun J
Lichtenstein Paul P
Lieberman Jeffrey A JA
Lin Dan-Yu DY
Linszen Don H DH
Liu Chunyu C
Lohoff Falk W FW
Loo Sandra K SK
Lord Catherine C
Lowe Jennifer K JK
Lucae Susanne S
MacIntyre Donald J DJ
Madden Pamela A F PA
Maestrini Elena E
Magnusson Patrik K E PK
Mahon Pamela B PB
Maier Wolfgang W
Malhotra Anil K AK
Mane Shrikant M SM
Martin Christa L CL
Martin Nicholas G NG
Mattheisen Manuel M
Matthews Keith K
Mattingsdal Morten M
McCarroll Steven A SA
McGhee Kevin A KA
McGough James J JJ
McGrath Patrick J PJ
McGuffin Peter P
McInnis Melvin G MG
McIntosh Andrew A
McKinney Rebecca R
McLean Alan W AW
McMahon Francis J FJ
McMahon William M WM
McQuillin Andrew A
Medeiros Helena H
Medland Sarah E SE
Meier Sandra S
Melle Ingrid I
Meng Fan F
Meyer Jobst J
Middeldorp Christel M CM
Middleton Lefkos L
Milanova Vihra V
Miranda Ana A
Monaco Anthony P AP
Montgomery Grant W GW
Moran Jennifer L JL
Moreno-De-Luca Daniel D
Morken Gunnar G
Morris Derek W DW
Morrow Eric M EM
Moskvina Valentina V
Mowry Bryan J BJ
Muglia Pierandrea P
Mühleisen Thomas W TW
Müller-Myhsok Bertram B
Murtha Michael M
Myers Richard M RM
Myin-Germeys Inez I
Neale Benjamin M BM
Nelson Stan F SF
Nievergelt Caroline M CM
Nikolov Ivan I
Nimgaonkar Vishwajit V
Nolen Willem A WA
Nöthen Markus M MM
Nurnberger John I JI
Nwulia Evaristus A EA
Nyholt Dale R DR
O'Donovan Michael C MC
O'Dushlaine Colm C
Oades Robert D RD
Olincy Ann A
Oliveira Guiomar G
Olsen Line L
Ophoff Roel A RA
Osby Urban U
Owen Michael J MJ
Palotie Aarno A
Parr Jeremy R JR
Paterson Andrew D AD
Pato Carlos N CN
Pato Michele T MT
Penninx Brenda W BW
Pergadia Michele L ML
Pericak-Vance Margaret A MA
Perlis Roy H RH
Pickard Benjamin S BS
Pimm Jonathan J
Piven Joseph J
Posthuma Danielle D
Potash James B JB
Poustka Fritz F
Propping Peter P
Purcell Shaun M SM
Puri Vinay V
Quested Digby J DJ
Quinn Emma M EM
Ramos-Quiroga Josep Antoni JA
Rasmussen Henrik B HB
Raychaudhuri Soumya S
Rehnström Karola K
Reif Andreas A
Ribasés Marta M
Rice John P JP
Rietschel Marcella M
Ripke Stephan S
Roeder Kathryn K
Roeyers Herbert H
Rossin Lizzy L
Rothenberger Aribert A
Rouleau Guy G
Ruderfer Douglas D
Rujescu Dan D
Sanders Alan R AR
Sanders Stephan J SJ
Santangelo Susan L SL
Schachar Russell R
Schalling Martin M
Schatzberg Alan F AF
Scheftner William A WA
Schellenberg Gerard D GD
Scherer Stephen W SW
Schork Nicholas J NJ
Schulze Thomas G TG
Schumacher Johannes J
Schwarz Markus M
Scolnick Edward E
Scott Laura J LJ
Sergeant Joseph A JA
Shi Jianxin J
Shilling Paul D PD
Shyn Stanley I SI
Silverman Jeremy M JM
Sklar Pamela P
Slager Susan L SL
Smalley Susan L SL
Smit Johannes H JH
Smith Erin N EN
Smoller Jordan W JW
Sonuga-Barke Edmund J S EJ
St Clair David D
State Matthew M
Steffens Michael M
Steinhausen Hans-Christoph HC
Strauss John S JS
Strohmaier Jana J
Stroup T Scott TS
Sullivan Patrick F PF
Sutcliffe James J
Szatmari Peter P
Szelinger Szabocls S
Thapar Anita A
Thirumalai Srinivasa S
Thompson Robert C RC
Todorov Alexandre A AA
Tozzi Federica F
Treutlein Jens J
Tzeng Jung-Ying JY
Uhr Manfred M
van den Oord Edwin J C G EJ
Van Grootheest Gerard G
Van Os Jim J
Vicente Astrid M AM
Vieland Veronica J VJ
Vincent John B JB
Visscher Peter M PM
Walsh Christopher A CA
Wassink Thomas H TH
Watson Stanley J SJ
Weiss Lauren A LA
Weissman Myrna M MM
Werge Thomas T
Wienker Thomas F TF
Wiersma Durk D
Wijsman Ellen M EM
Willemsen Gonneke G
Williams Nigel N
Willsey A Jeremy AJ
Witt Stephanie H SH
Wray Naomi R NR
Xu Wei W
Young Allan H AH
Yu Timothy W TW
Zammit Stanley S
Zandi Peter P PP
Zhang Peng P
Zitman Frans G FG
Zöllner Sebastian S
JOURNAL
VOLUME: 96
ISSUE: 2
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2015
MONTH: Feb
DAY: 5
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
104036 Wellcome Trust United Kingdom
P30 CA016359 NCI NIH HHS United States
R01 MH059541 NIMH NIH HHS United States
R01 MH059542 NIMH NIH HHS United States
R01 MH059552 NIMH NIH HHS United States
R01 MH060912 NIMH NIH HHS United States
R01 MH061686 NIMH NIH HHS United States
R01 MH075131 NIMH NIH HHS United States
R01 MH077139 NIMH NIH HHS United States
R01 MH094293 NIMH NIH HHS United States
R25 MH060482 NIMH NIH HHS United States
U01 MH085520 NIMH NIH HHS United States
UL1 TR000142 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Bipolar Disorder genetics
Depressive Disorder, Major genetics
Genetic Testing methods
Genetics, Medical methods
Humans methods
Linear Models methods
Mental Disorders genetics
Multifactorial Inheritance genetics
Multivariate Analysis genetics
Polymorphism, Single Nucleotide genetics
Risk Assessment methods
Schizophrenia genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC4320268 NLM