Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q.
Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches.
McQueen
Matthew B
MB
Harvard School of Public Health, Department of Epidemiology, Boston, MA 02115, USA. mmcqueen@hsph.harvard.edu
Devlin
B
B
Faraone
Stephen V
SV
Nimgaonkar
Vishwajit L
VL
Sklar
Pamela
P
Smoller
Jordan W
JW
Abou Jamra
Rami
R
Albus
Margot
M
Bacanu
Silviu-Alin
SA
Baron
Miron
M
Barrett
Thomas B
TB
Berrettini
Wade
W
Blacker
Deborah
D
Byerley
William
W
Cichon
Sven
S
Coryell
Willam
W
Craddock
Nick
N
Daly
Mark J
MJ
Depaulo
J Raymond
JR
Edenberg
Howard J
HJ
Foroud
Tatiana
T
Gill
Michael
M
Gilliam
T Conrad
TC
Hamshere
Marian
M
Jones
Ian
I
Jones
Lisa
L
Juo
Suh-Hang
SH
Kelsoe
John R
JR
Lambert
David
D
Lange
Christoph
C
Lerer
Bernard
B
Liu
Jianjun
J
Maier
Wolfgang
W
Mackinnon
James D
JD
McInnis
Melvin G
MG
McMahon
Francis J
FJ
Murphy
Dennis L
DL
Nothen
Markus M
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Nurnberger
John I
JI
Pato
Carlos N
CN
Pato
Michele T
MT
Potash
James B
JB
Propping
Peter
P
Pulver
Ann E
AE
Rice
John P
JP
Rietschel
Marcella
M
Scheftner
William
W
Schumacher
Johannes
J
Segurado
Ricardo
R
Van Steen
Kristel
K
Xie
Weiting
W
Zandi
Peter P
PP
Laird
Nan M
NM
D001714:Bipolar Disorder / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans