W46. CO-HERITABILITY OF BIPOLAR DISORDER AND DIMENSIONS OF PSYCHOPATHOLOGY WITHIN FAMILIES

Bipolar disorder (BD) is known to be highly heritable. Relatives of those with BD have been observed to experience a range of psychiatric symptoms, yet the extent to which particular symptoms reflect BD risk genes is largely unknown. To address this question, we are investigating the co-heritability of BD and nine dimensions of psychopathology in a family sample. Affected probands and their family members enrolled in the Amish Mennonite Bipolar Genetics (AmBiGen) study completed the Symptom Checklist Questionnaire Revised (SCL-90-R), which measures 9 dimensions of psychopathology. Each participant was assigned a Best Estimate Final Diagnosis (BEFD) using one or more of the following: Diagnostic Interview for Genetics Studies (DIGS), Family Interview for Genetic Studies (FIGS), medical records, Mood Disorder Questionnaire, Past History Schedule, and SCL-90-R. Of the 501 participants, 224 were determined to be unaffected by any mental health disorder, 122 were determined to be affected with BP, and 155 were determined to be affected with one or more other mental health diagnoses. Participants’ genotypes were determined via SNP array genotyping. Polygenic risk scores (PRS) were calculated through published genome-wide association studies (GWAS) in independent samples. The heritability and co-heritability of psychopathological dimensions will be assessed through Sequential Oligogenic Linkage Analysis Routines (SOLAR) and the Genomic Relationship Matrix (GRM). The association between psychopathological dimensions and PRS for BP and various other psychiatric traits will also be assessed. Preliminary results indicate a broad range of psychopathology in this high-risk sample. Compared to healthy participants, those affected with BD or related disorders showed elevated scores for all dimensions of psychopathology, especially obsessive-compulsive traits, depression, and interpersonal sensitivity. It is expected that some of these dimensions will be co-heritable with BD or other disorders. PRS associations may align with co-heritability findings, while differences could reflect rare risk alleles. Since genetic risk for BD is expressed differently across individuals, some psychopathological dimensions could be more related to genetic risk for BD, while others may reflect distinct risk profiles, such as other genetic risk factors, comorbidity, and life experiences. Determining the phenotypes associated with genetic risk for BD in those with and without a BD diagnosis will give a clearer understanding of how genetic risk of BD is expressed among relatives and which symptoms may be most predictive of BD among high-risk individuals.