Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: fine mapping adds support on chromosomes 6 and 11.
As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107-114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 (P = 0.025) with the same marker D6S1021(104.7 Mb). Higher-density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 (P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 (P = 0.0019). A similar pattern was detected with higher-density mapping of chromosome 11 with an NPL = 3.15 (P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome-wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans. Published 2004 Wiley-Liss, Inc.
Pato
Carlos N
CN
Veterans Affairs Medical Center, Washington, DC 20422, USA. cmpato@aol.com
Pato
M T
MT
Kirby
A
A
Petryshen
T L
TL
Medeiros
H
H
Carvalho
C
C
Macedo
A
A
Dourado
A
A
Coelho
I
I
Valente
J
J
Soares
M J
MJ
Ferreira
C P
CP
Lei
M
M
Verner
A
A
Hudson
T J
TJ
Morley
C P
CP
Kennedy
J L
JL
Azevedo
M H
MH
Daly
M J
MJ
Sklar
P
P
D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005192:Family Health; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats; D011174:Portugal