Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20.
OBJECTIVE
Our aim is to map chromosomal regions that harbor loci that increase susceptibility to bipolar disorder.


METHODS
We analyzed 644 bipolar families ascertained by the National Institute of Mental Health Human Genetics Initiative for bipolar disorder. The families have been genotyped with microsatellite loci spaced every approximately 10 cM or less across the genome. Earlier analyses of these pedigrees have been limited to nonparametric (model-free) methods and thus, information from unaffected subjects with genotypes was not considered. In this study, we used parametric analyses assuming dominant and recessive transmission and specifying a maximum penetrance of 70%, so that information from unaffecteds could be weighed in the linkage analyses. As in previous linkage analyses of these pedigrees, we analyzed three diagnostic categories: model 1 included only bipolar I and schizoaffective, bipolar cases (1565 patients of whom approximately 4% were schizoaffective, bipolar); model 2 included all individuals in model 1 plus bipolar II patients (1764 total individuals); and model 3 included all individuals in model 2 with the addition of patients with recurrent major depressive disorder (2046 total persons).


RESULTS
Assuming dominant inheritance the highest genome-wide pair-wise logarithm of the odds (LOD) score was 3.2 with D16S749 using model 2 patients. Multipoint analyses of this region yielded a maximum LOD score of 4.91. Under recessive transmission a number of chromosome 20 markers were positive and multipoint analyses of the area gave a maximum LOD of 3.0 with model 2 cases.


CONCLUSIONS
The chromosome 16p and 20 regions have been implicated by some studies and the data reported herein provide additional suggestive evidence of bipolar susceptibility genes in these regions.
Ross
Jessica
J
Department of Psychiatry, University of California, San Francisco, CA 94132-0984, USA.
Berrettini
Wade
W
Coryell
William
W
Gershon
Elliot S
ES
Badner
Judith A
JA
Kelsoe
John R
JR
McInnis
Melvin G
MG
McMahon
Francis J
FJ
Murphy
Dennis L
DL
Nurnberger
John I
JI
Foroud
Tatiana
T
Rice
John P
JP
Scheftner
William B
WB
Zandi
Peter
P
Edenberg
Howard
H
Byerley
William
W
D001714:Bipolar Disorder / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D010375:Pedigree