Tiffany A Greenwood1, Judith A Badner2, William Byerley3, Paul E Keck4, Susan L McElroy5, Ronald A Remick6, A Dessa Sadovnick7, John R Kelsoe8. 1. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, Mail Code 0737, La Jolla, CA 92093, USA. Electronic address: tgreenwood@ucsd.edu. 2. Department of Psychiatry, University of Chicago, Chicago, IL, USA. 3. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA. 4. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA. 5. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. 6. St. Paul's Hospital, Vancouver, Canada. 7. University of British Columbia, Vancouver, Canada. 8. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, Mail Code 0737, La Jolla, CA 92093, USA; San Diego Veterans Affairs Healthcare System, San Diego, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Abstract
BACKGROUND: The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST). METHODS: We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available. RESULTS: Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12). LIMITATIONS: The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study. CONCLUSIONS: While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility.
BACKGROUND: The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST). METHODS: We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available. RESULTS: Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12). LIMITATIONS: The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study. CONCLUSIONS: While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility.
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