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
12802785
TITLE
Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.
ABSTRACT
Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.
DATE PUBLISHED
2003 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2003/06/13 05:00
medline 2003/08/13 05:00
received 2002/00/23
accepted 2003/00/09
aheadofprint 2003/00/11
entrez 2003/06/13 05:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Segurado R Segurado Ricardo R Neuropsychiatric Genetics Unit, Department of Genetics, Trinity College, Dublin 2, Ireland. seguradr@tcd.ie
Detera-Wadleigh SD Detera-Wadleigh Sevilla D SD
Levinson DF Levinson Douglas F DF
Lewis CM Lewis Cathryn M CM
Gill M Gill Michael M
Nurnberger JI Jr Nurnberger John I JI
Craddock N Craddock Nick N
DePaulo JR DePaulo J Raymond JR
Baron M Baron Miron M
Gershon ES Gershon Elliot S ES
Ekholm J Ekholm Jenny J
Cichon S Cichon Sven S
Turecki G Turecki Gustavo G
Claes S Claes Stephan S
Kelsoe JR Kelsoe John R JR
Schofield PR Schofield Peter R PR
Badenhop RF Badenhop Renee F RF
Morissette J Morissette J J
Coon H Coon Hilary H
Blackwood D Blackwood Douglas D
McInnes LA McInnes L Alison LA
Foroud T Foroud Tatiana T
Edenberg HJ Edenberg Howard J HJ
Reich T Reich Theodore T
Rice JP Rice John P JP
Goate A Goate Alison A
McInnis MG McInnis Melvin G MG
McMahon FJ McMahon Francis J FJ
Badner JA Badner Judith A JA
Goldin LR Goldin Lynn R LR
Bennett P Bennett Phil P
Willour VL Willour Virginia L VL
Zandi PP Zandi Peter P PP
Liu J Liu Jianjun J
Gilliam C Gilliam Conrad C
Juo SH Juo Suh-Hang SH
Berrettini WH Berrettini Wade H WH
Yoshikawa T Yoshikawa Takeo T
Peltonen L Peltonen Leena L
Lönnqvist J Lönnqvist Jouko J
Nöthen MM Nöthen Markus M MM
Schumacher J Schumacher Johannes J
Windemuth C Windemuth Christine C
Rietschel M Rietschel Marcella M
Propping P Propping Peter P
Maier W Maier Wolfgang W
Alda M Alda Martin M
Grof P Grof Paul P
Rouleau GA Rouleau Guy A GA
Del-Favero J Del-Favero Jurgen J
Van Broeckhoven C Van Broeckhoven Christine C
Mendlewicz J Mendlewicz Julien J
Adolfsson R Adolfsson Rolf R
Spence MA Spence M Anne MA
Luebbert H Luebbert Hermann H
Adams LJ Adams Linda J LJ
Donald JA Donald Jennifer A JA
Mitchell PB Mitchell Philip B PB
Barden N Barden Nicholas N
Shink E Shink Eric E
Byerley W Byerley William W
Muir W Muir Walter W
Visscher PM Visscher Peter M PM
Macgregor S Macgregor Stuart S
Gurling H Gurling Hugh H
Kalsi G Kalsi Gursharan G
McQuillin A McQuillin Andrew A
Escamilla MA Escamilla Michael A MA
Reus VI Reus Victor I VI
Leon P Leon Pedro P
Freimer NB Freimer Nelson B NB
Ewald H Ewald Henrik H
Kruse TA Kruse Torben A TA
Mors O Mors Ole O
Radhakrishna U Radhakrishna Uppala U
Blouin JL Blouin Jean-Louis JL
Antonarakis SE Antonarakis Stylianos E SE
Akarsu N Akarsu Nurten N
INVESTIGATORS
JOURNAL
VOLUME: 73
ISSUE: 1
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2003
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
1R01 MH 3448 NIMH NIH HHS United States
G9309834 Medical Research Council United Kingdom
G9810900 Medical Research Council United Kingdom
K02 MH 01089 NIMH NIH HHS United States
K24 MH 064197 NIMH NIH HHS United States
M01 RR 00827 NCRR NIH HHS United States
MH 00176 NIMH NIH HHS United States
MH 01099 NIMH NIH HHS United States
MH 42243 NIMH NIH HHS United States
MH 42535 NIMH NIH HHS United States
MH 43979 NIMH NIH HHS United States
MH 47612 NIMH NIH HHS United States
MH 59553 NIMH NIH HHS United States
MH 59567 NIMH NIH HHS United States
MH 63876 NIMH NIH HHS United States
N01 HG 65493 NHGRI NIH HHS United States
R01 MH 042463 NIMH NIH HHS United States
R01 MH 42643 NIMH NIH HHS United States
R01 MH 49499 NIMH NIH HHS United States
R01 MH 59545 NIMH NIH HHS United States
R01 MH 62276 NIMH NIH HHS United States
R01 NS 37484 NINDS NIH HHS United States
U01 MH 54723 NIMH NIH HHS United States
U01 MH 46274 NIMH NIH HHS United States
U01 MH 46280 NIMH NIH HHS United States
U01 MH 46282 NIMH NIH HHS United States
U01 MH 54701 NIMH NIH HHS United States
U01 MH 54794 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Bipolar Disorder genetics
Genome, Human genetics
Humans genetics
Schizophrenia genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC1180589 NLM