There is a paucity of genome-wide association study on Han Chinese gout patients. We performed a genome-wide association meta-analysis on two Taiwanese cohorts consisting of 758 gout cases and 14166 controls of Han Chinese ancestry. All the participants were recruited from the Taiwan Biobank. For pathway analysis, we applied ICSNPathway (Identify candidate Causal SNPs and Pathways) analysis, and to investigate whether expression-associated genetic variants contribute to gout susceptibility, we systematically integrated lymphoblastoid expression quantitative trait loci (eQTL) and genome-wide association data of gout using Sherlock, a Bayesian statistical frame-work. In the meta-analysis, we found 4 SNPs that reached genome-wide statistical significance (P < 5.0 × 10−8). These SNPs are in or close to ABCG2, PKD2 and NUDT9 gene on chromosome 4. ICSNPathway analysis identified rs2231142 as the candidate causal SNP, and ABCG2 as the candidate gene. Sherlcok analysis identified three genes, which were significantly associated with the risk of gout (PKD2, NUTD9, and NAP1L5). To conclude, we reported novel susceptible loci for gout that has not been previously addressed in the literature.
We characterized the heterogeneity and risk factors of cognitive decline in euthymic bipolar disorder (BD), and their magnitude of associations with subjective daily functions. In this retrospective cohort, BD type I patients (N = 128) were followed for an average of 6.5 years. Intelligence quotient (IQ) at index date was recorded, and premorbid IQ was estimated. We used Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognition at follow-up. We evaluated current functions with World Health Organization Disability Assessment Schedule 2.0. Clinical and sociodemographic factors were examined for their independent effects on longitudinal cognitive decline. In addition, we employed multivariate adaptive regression spline to detect inflection points for the nature of slope changes in cognitive decline among BD patients. During follow-up years, 21 BD patients (16.4%) showed longitudinal cognitive decline. In cognitive decline group, all cognitive domains of BAC-A were significantly worsened. We found that density of episodes with psychotic features was an independent risk factor for cognitive decline after adjusted for age, gender and dose of mood stabilizer. After the age of 42 years, a steeper cognitive change was observed in the cognitive decline group. The correlation pattern between cognitive domains and functional outcomes differed between patients with and without cognitive decline. The present study characterized cognitive heterogeneity longitudinally in BD patients. As density of episodes play roles for cognitive decline, our results emphasize the importance of relapse prevention. Our findings provide hints for future personalized interventions and facilitating genetic and biological studies for dissecting the heterogeneity of bipolar illness.
Background: We characterized the heterogeneity and risk factors of cognitive decline in bipolar disorder (BD), and their magnitude of associations with subjective daily functions. Methods: Recruited BD patients (N=127) were followed for an average of 6.5 years. Baseline intelligence quotient was measured, and Brief Assessment of Cognition in Affective Disorders (BAC-A) was used to assess cognition at follow-up. We evaluated current functions with World Health Organization Disability Assessment Schedule 2.0. Clinical and sociodemographic factors were compared between BD patients with and without longitudinal cognitive decline and revealed the independent risk factors through multiple regression analysis. Correlations between specific cognitive domains and functional outcomes were examined in subgroups of BD.Results: Overall, 32.3% of BD patients showed longitudinal cognitive decline. In cognitive decline group, all cognitive domains of BAC-A were significantly worsened. Baseline independent risk factors for cognitive decline were older age, body mass index >25, and manic episode density during the disease course. After the age of 40 years, a steeper cognitive change was observed in the cognitive decline group. Housekeeping dysfunction was the most sensitive function related to diverse cognitive impairment in cognitive decline group. The correlations between cognitive domains and functional outcomes differed between patients with and without cognitive decline.Conclusions: This study characterized cognitive heterogeneity longitudinally in BD, as the foundation to facilitate future genetic and biological studies for BD subtypes. Manic episode density and overweight are important risk factors for cognitive decline; therefore, we suggested further interventions should target on relapse prevention and controlling body weight.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.