國家衛生研究院 NHRI:Item 3990099045/11872
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    题名: Identifying variants in nf1a gene to be associated with seasonal pattern and susceptibility for depression through a candidate gene approach
    作者: Fan, TY;Huang, MC;Lu, ML;Chen, HC;Tsai, SJ;Liu, YL;Chen, CH;Kuo, PH
    贡献者: Center for Neuropsychiatric Research
    摘要: Background: Seasonal Pattern (SP) was reported in depressive patients of both Bipolar Disorder (BD) and Major Depressive Disorder (MDD). In this study, we aimed to investigate genetic contributions of seasonal pattern of major depressive episodes in both BD and MDD patients, including genes in relevant biological pathways indicated in previous studies. To further clarify the roles of the variants in depression, we conducted analyses using a case-control study design to examine whether the genetic variants for SP also possess effects on susceptibility to depression. Methods: We recruited 472 BD (83%) and MDD (17%) patients in Taiwan. SP of depressive episode were defined according to interview questions as “Which season do you feel the worst?” in their first, the most serious, and the most recent episode within a year. Subjects answered a specific season in two of the three episode categories were considered SP+, while others were categorized as non-SP (SP-). The other dataset for depression was obtained from the Taiwan biobank with about 10,000 people. Cases were defined by self-report MDD history or having the sum-score greater than 3 in the Patient Health Questionnaire-4. We examined 15 genes (824 single nucleotide variants) including the melatonin pathway (MTNR1a, MTNR1b, AANAT), serotonin pathway (TPH2, HTR2A, HTR2B, SLC6A4), circadian feedback loop (NPAS2, CRY2, ARNTL, ARNTL2, RORA, RORB, PER) and NF1A gene that identified from a previous genome-wide association study of seasonal mania. Association analyses were performed by multivariate logistic regression, adjusting for gender, age, and diagnosis. We corrected for multiple testings using false discovery rate method. Results: After excluding subjects with missing covariates, there were a total of 464 subjects with 162 (35%) in the SP+ and 302 (65%) in the SP- groups. No differences were observed in gender, age or diagnosis distribution between the two SP groups. Nominal associations with p-valueo0.01 was observed in 20 markers for SP of depressive episodes, 19 of them located in NFA1 gene and 1 locus in RORA gene. Marker rs1547849 in the NFA1 gene showed the highest significant level (P=6.37n10-5), followed by rs1777546 (P=1.52n10-4) and rs1779868 (P=1.83n10-4). These genetic variants remained significant (P-values=0.05) after multiple testing correction. The 20 markers were tested again for depression in 9862 individuals from Taiwan biobank. Although none of them showed genome-wide significance, 6 SNPs had nominal p-valueso0.05, and rs334724 in NFA1gene had the smallest p-value (P=1.08n10-3). Discussion: We found that NF1A gene maybe a susceptible gene for depression and modifiable gene for SP. Some genetic variants in this gene are related to both seasonal pattern of depressive episodes and depression with nominal significance, indicating partially shared genetic components between the development of mood symptoms and seasonality in depression. Further investigation is needed for replication with more stringent seasonal pattern evaluation, and for exploring the exact biological functions of the identified genetic variants.
    日期: 2019-01
    關聯: European Neuropsychopharmacology. 2019 Jan;29(Suppl. 3):S857-S858.
    Link to: http://dx.doi.org/10.1016/j.euroneuro.2017.08.137
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0924-977X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000462156400266
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