Dense SNP association study for bipolar I disorder on chromosome 18p11 suggests two loci with excess paternal transmission

• Published in: Molecular psychiatry Vol. 12; no. 4; pp. 367 - 375
• Main Authors: MULLE, J. G, FALLIN, M. D, LASSETER, V. K, MCGRATH, J. A, WOLYNIEC, P. S, PULVER, A. E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.2007
• Subjects: Adult and adolescent clinical studies; Alleles; Behavioral sciences; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - genetics; Bipolar disorders; Chromosome 18; Chromosomes; Chromosomes, Human, Pair 18; Disease; Family Health; Father-Child Relations; Female; Gene Frequency; Genes; Genetic Predisposition to Disease; Genomes; Genotype; Genotyping; Haplotypes; Humans; Hypotheses; Jews; Linkage Disequilibrium; Longitudinal Studies; Male; Medical sciences; Medicine; Mood disorders; Phenotypes; Polymorphism, Single Nucleotide - genetics; Population studies; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Single-nucleotide polymorphism; Statistical analysis; Susceptibility; United States > US; Baltimore Maryland; Mood disorder; transmission disequilibrium; parent of origin; psychiatric genetics; 18p11; Parent; genetic association; Genetics; Bipolar disorder
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001916

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.