Dense SNP association study for bipolar I disorder on chromosome 18p11 suggests two loci with excess paternal transmission.
Parent-of-origin effects have been implicated as mediators of genetic susceptibility for a number of complex disease phenotypes, including bipolar disorder. Specifically, evidence for linkage on chromosome 18 is modified when allelic parent-of-origin is accommodated in the analysis. Our goal was to characterize the susceptibility locus for bipolar I disorder on chromosome 18p11 and investigate this parent-of-origin hypothesis in an association context. This was achieved by genotyping single nucleotide polymorphisms (SNPs) at a high density (1 SNP/5 kb) along 13.6 megabases of the linkage region. To increase our ability to detect a susceptibility locus, we restricted the phenotype definition to include only bipolar I probands. We also restricted our study population to Ashkenazi Jewish individuals; this population has characteristics of a genetic isolate and may therefore facilitate detection of variants for complex disease. Three hundred and forty-four pedigrees (363 parent/child trios) where probands were affected with bipolar 1 disorder were genotyped. Transmission disequilibrium test analysis revealed no statistically significant association to SNPs or haplotypes within this region in this sample. However, when parent-of-origin of transmitted SNPs was taken into account, suggestive association was revealed for two separate loci.
Mulle
J G
JG
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Fallin
M D
MD
Lasseter
V K
VK
McGrath
J A
JA
Wolyniec
P S
PS
Pulver
A E
AE
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D005192:Family Health; D005219:Father-Child Relations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007585:Jews; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*