Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative.
We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.
Dick
Danielle M
DM
Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA.
Foroud
Tatiana
T
Flury
Leah
L
Bowman
Elizabeth S
ES
Miller
Marvin J
MJ
Rau
N Leela
NL
Moe
P Ryan
PR
Samavedy
Nalini
N
El-Mallakh
Rif
R
Manji
Husseini
H
Glitz
Debra A
DA
Meyer
Eric T
ET
Smiley
Carrie
C
Hahn
Rhoda
R
Widmark
Clifford
C
McKinney
Rebecca
R
Sutton
Laura
L
Ballas
Christos
C
Grice
Dorothy
D
Berrettini
Wade
W
Byerley
William
W
Coryell
William
W
DePaulo
Raymond
R
MacKinnon
Dean F
DF
Gershon
Elliot S
ES
Kelsoe
John R
JR
McMahon
Francis J
FJ
McInnis
Melvin
M
Murphy
Dennis L
DL
Reich
Theodore
T
Scheftner
William
W
Nurnberger
John I
JI
D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005824:Genetics, Behavioral; D015894:Genome, Human; D006801:Humans; D008297:Male; D009316:National Institutes of Health (U.S.); D010375:Pedigree; D014481:United States