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• W4387476733 abstract "The underlying mechanisms responsible for the seasonal affective features (SA) observed in patients with mood disorders (MD) are still not fully understood. Various hypotheses have been proposed to explain the seasonal adaptation in MD patients with a recognized role of genetics in the pathophysiology of MD. However, few studies have directly examined the genetic impact of seasonality in MD, including only two genome-wide association studies (GWAS) specifically focusing on seasonal patterns in MD. Thus, our goal was to contribute to the understanding of genetic factors associated with seasonality in MD by conducting a GWAS to identify relevant loci. A total of 1065 subjects, consisting of 477 MD patients and 588 healthy controls (HC), were included in the GWAS analysis. MD patients were divided into two groups according to the global seasonality score (GSS) obtained from the Seasonal Pattern Assessment Questionnaire: SA (n = 125) and NSA (n = 352), for which the SA was defined by having a GSS score ≥ 11 along with a moderate level of disturbances due to seasonal fluctuation. We performed GWA analysis with three different dependent variables in three models, linear regression for the GSS in all subjects, and logistic regression for SA v.s NSA and SA v.s HC, respectively. All models were adjusted for age, sex, and the first three principal components. The model 1 and 2 were further adjusted for diagnoses of MD. The significance threshold was set at a p-value < 5 × 10-8, while a p-value < 5 × 10-6 was considered suggestive of association. We further conducted the gene-based analysis by examining KEGG “circadian rhythm (hsa04710)” pathway. Regional association plots were generated using the online web tool LocusZoom. In our analysis of continuous GSS, we identified a locus rs146370530 (p = 5.05 × 10-8) on chromosome 1, which mapped to the USH2A gene. However, when analyzing categorical SA definitions, no SNPs reached the threshold for genome-wide significance in both models. Nevertheless, after conducting LD clumping, several SNPs showed suggestive significance. Notably, both models 2 and 3 revealed an overlapping lead SNP, rs10810641 on chromosome 9, which was mapped to the BNC2 gene. This SNP was identified as a susceptibility locus for patients with SA compared to both those with NSA (odds ratio, OR = 3.107, p = 2.14 × 10-6) and healthy controls (OR = 2.897, p = 9.66 × 10-7). Additionally, in the gene-based analysis, we observed that the PRKAA1 gene (empirical p = 0.007) had an impact on MD patients with SA compared to those with NSA. Similar results were obtained in model 3, with PRKAA1 (empirical p = 0.001) being the most significant gene in the SA versus HC comparison. In the current study conducted in Taiwan, a subtropical country, the GWA results revealed that the USH2A, BNC2, and PRKAA1 genes might play a role in the development of seasonal affective features in patients with MD. The USH2A (Usherin), is involved in the development and homeostasis of the inner ear and retina through its role in the basement membrane. While there is no direct evidence linking USH2A mutations to SA, previous studies have reported abnormalities in retina sensitivity in individuals with seasonal affective disorder. Further research is needed to confirm these associations in independent samples with comprehensive phenotype data." @default.
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• W4387476733 date "2023-10-01" @default.
• W4387476733 modified "2023-10-16" @default.
• W4387476733 title "T33. EXPLORATION OF GENETIC RISK VARIANTS OF MOOD DISORDER PATIENTS WITH SEASONAL AFFECTIVE FEATURE" @default.
• W4387476733 doi "https://doi.org/10.1016/j.euroneuro.2023.08.319" @default.
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