Genomewide scan and fine-mapping linkage studies in four European samples with bipolar affective disorder suggest a new susceptibility locus on chromosome 1p35-p36 and provides further evidence of loci on chromosome 4q31 and 6q24.
We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German families (280 individuals) was included for this fine-mapping step. The highest nonparametric linkage scores obtained in the fine mapping were 5.49 for 4q31 and 4.87 for 6q24 in the Romany families and 3.97 for 1p35-p36 in the Spanish sample. MOD-score (LOD scores maximized over genetic model parameters) analysis provided significant evidence of linkage to 4q31 and at least borderline significance for the 1p and 6q regions. On the basis of these results and previous positive research findings, 4q31 and 6q24 should now be considered confirmed BPAD susceptibility loci, and 1p35-p36 is proposed as a new putative locus that requires confirmation in replication studies.
Schumacher
Johannes
J
Institute of Human Genetics, Life & Brain Center, University of Bonn, D-53105 Bonn, Germany.
Kaneva
Radka
R
Jamra
Rami Abou
RA
Diaz
Guillermo Orozco
GO
Ohlraun
Stephanie
S
Milanova
Vihra
V
Lee
Young-Ae
YA
Rivas
Fabio
F
Mayoral
Fermin
F
Fuerst
Robert
R
Flaquer
Antonia
A
Windemuth
Christine
C
Gay
Eudoxia
E
Sanz
Sebastian
S
González
Maria José
MJ
Gil
Susana
S
Cabaleiro
Francisco
F
del Rio
Francisco
F
Perez
Fermin
F
Haro
Jesus
J
Kostov
Christian
C
Chorbov
Vesselin
V
Nikolova-Hill
Amelia
A
Stoyanova
Vessela
V
Onchev
George
G
Kremensky
Ivo
I
Strauch
Konstantin
K
Schulze
Thomas G
TG
Nürnberg
Peter
P
Gaebel
Wolfgang
W
Klimke
Ansgar
A
Auburger
Georg
G
Wienker
Thomas F
TF
Kalaydjieva
Luba
L
Propping
Peter
P
Cichon
Sven
S
Jablensky
Assen
A
Rietschel
Marcella
M
Nöthen
Markus M
MM
D001714:Bipolar Disorder / Q000235:genetics; D002031:Bulgaria / Q000208:ethnology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005858:Germany / Q000208:ethnology; D006801:Humans; D008126:Lod Score; D020161:Physical Chromosome Mapping; D006178:Romani People / Q000208:ethnology; D013030:Spain / Q000208:ethnology; D044465:White People / Q000208:ethnology / Q000706:statistics & numerical data
D005819:Genetic Markers