A Pharmcogenetic Study of Bipolar Disorder in a Taiwanese Han Chinese Population (TWBP)

Objective: To identify genetic variants associated with response to lithium prophylaxis treatment. Materials: 294 bipolar I (BPI) patients receiving lithium treatment, a subset of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. Lithium response was assessed based on the Alda Scale. Methods: Responders to lithium treatment were defined if the patients' Alda Scale > 4, 5, 6, and 7. Genome-wide association (GWA) analysis was carried out on the 294 BPI patients for the 4 definitions of responders. The SNPs showing strongest association in the GWAS were then tested for association in a replication sample of 100 patients and further tested in a prospective follow-up series of 24 patients. Results: Two SNPs on GADL1 showed the strongest associations in the four GWA analyses and in the replication set of 100 patients. These two SNPs had a sensitivity of 0.93 for predicting lithium response and differentiated between the good and poor responders in the follow-up cohort. Summary: These genetic variants are associated with response to lithium prophylaxis treatment for BPI.]]>
A total of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. We genotyped the 1647 participants using Illumina HumanHap550-Duo BeadChip and HumanOmni1-Quad BeadChip and integrated through imputation with HapMap Phase 2 data. Lithium treatment response was assessed based on the Alda Scale. The association results presented here are from a genome-wide association analysis of 294 BPI patients receiving lithium treatment. The median age of the participant was 49 years old and males and females were similar in proportion. The GWA analysis was performed uisng a cutoff point of Alda Scale at 4/5 for classifying subjects with, respectively, greater than 50% reduction of illness activity as responders in lithium prophylaxis treatment.A total of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. We genotyped the 1647 participants using Illumina HumanHap550-Duo BeadChip and HumanOmni1-Quad BeadChip and integrated through imputation with HapMap Phase 2 data. Lithium treatment response was assessed based on the Alda Scale. The association results presented here are from a genome-wide association analysis of 294 BPI patients receiving lithium treatment. The median age of the participant was 49 years old and males and females were similar in proportion. The GWA analysis was performed uisng a cutoff point of Alda Scale at 5/6 for classifying subjects with, respectively, greater than 65% reduction of illness activity as responders in lithium prophylaxis treatment.A total of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. We genotyped the 1647 participants using Illumina HumanHap550-Duo BeadChip and HumanOmni1-Quad BeadChip and integrated through imputation with HapMap Phase 2 data. Lithium treatment response was assessed based on the Alda Scale. The association results presented here are from a genome-wide association analysis of 294 BPI patients receiving lithium treatment. The median age of the participant was 49 years old and males and females were similar in proportion. The GWA analysis was performed uisng a cutoff point of Alda Scale at 6/7 for classifying subjects with, respectively, greater than 80% reduction of illness activity as responders in lithium prophylaxis treatment.A total of 1761 bipolar I (BPI) patients recruited by the Taiwan Bipolar Consortium. We genotyped the 1647 participants using Illumina HumanHap550-Duo BeadChip and HumanOmni1-Quad BeadChip and integrated through imputation with HapMap Phase 2 data. Lithium treatment response was assessed based on the Alda Scale. The association results presented here are from a genome-wide association analysis of 294 BPI patients receiving lithium treatment. The median age of the participant was 49 years old and males and females were similar in proportion. The GWA analysis was performed uisng a cutoff point of Alda Scale at 7/8 for classifying subjects with, respectively, greater than 90% reduction of illness activity as responders in lithium prophylaxis treatmentAll of these patients were diagnosed according to DSM-IV criteria for BPI with recurrent episodes of mania with or without depressive episode(s). The patients had received lithium prophylaxis treatment with good adherence for at least two years. Patients with other psychotic and affective disorders were excluded. The phenotype of lithium response was assessed based on the life chart, using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder developed by Martin Alda and Colleagues (Alda Scale).]]>