Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.
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.
Segurado
Ricardo
R
Neuropsychiatric Genetics Unit, Department of Genetics, Trinity College, Dublin 2, Ireland. seguradr@tcd.ie
Detera-Wadleigh
Sevilla D
SD
Levinson
Douglas F
DF
Lewis
Cathryn M
CM
Gill
Michael
M
Nurnberger
John I
JI
Craddock
Nick
N
DePaulo
J Raymond
JR
Baron
Miron
M
Gershon
Elliot S
ES
Ekholm
Jenny
J
Cichon
Sven
S
Turecki
Gustavo
G
Claes
Stephan
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Kelsoe
John R
JR
Schofield
Peter R
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Badenhop
Renee F
RF
Morissette
J
J
Coon
Hilary
H
Blackwood
Douglas
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McInnes
L Alison
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Foroud
Tatiana
T
Edenberg
Howard J
HJ
Reich
Theodore
T
Rice
John P
JP
Goate
Alison
A
McInnis
Melvin G
MG
McMahon
Francis J
FJ
Badner
Judith A
JA
Goldin
Lynn R
LR
Bennett
Phil
P
Willour
Virginia L
VL
Zandi
Peter P
PP
Liu
Jianjun
J
Gilliam
Conrad
C
Juo
Suh-Hang
SH
Berrettini
Wade H
WH
Yoshikawa
Takeo
T
Peltonen
Leena
L
Lönnqvist
Jouko
J
Nöthen
Markus M
MM
Schumacher
Johannes
J
Windemuth
Christine
C
Rietschel
Marcella
M
Propping
Peter
P
Maier
Wolfgang
W
Alda
Martin
M
Grof
Paul
P
Rouleau
Guy A
GA
Del-Favero
Jurgen
J
Van Broeckhoven
Christine
C
Mendlewicz
Julien
J
Adolfsson
Rolf
R
Spence
M Anne
MA
Luebbert
Hermann
H
Adams
Linda J
LJ
Donald
Jennifer A
JA
Mitchell
Philip B
PB
Barden
Nicholas
N
Shink
Eric
E
Byerley
William
W
Muir
Walter
W
Visscher
Peter M
PM
Macgregor
Stuart
S
Gurling
Hugh
H
Kalsi
Gursharan
G
McQuillin
Andrew
A
Escamilla
Michael A
MA
Reus
Victor I
VI
Leon
Pedro
P
Freimer
Nelson B
NB
Ewald
Henrik
H
Kruse
Torben A
TA
Mors
Ole
O
Radhakrishna
Uppala
U
Blouin
Jean-Louis
JL
Antonarakis
Stylianos E
SE
Akarsu
Nurten
N
D001714:Bipolar Disorder / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*