Wang Yi-Guang, Huang Chih-Chung, Yeh Ta-Chuan, Chen Wan-Ting, Chang Wei-Chou, Singh Ajeet B, Yeh Chin-Bin, Hung Yi-Jen, Hung Kuo-Sheng, Chang Hsin-An
Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan.
Department of Radiology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan.
Medicina (Kaunas). 2025 Mar 11;61(3):486. doi: 10.3390/medicina61030486.
In recent years, bipolar disorder (BD), a multifaceted mood disorder marked by severe episodic mood fluctuations, has been shown to have an impact on disability-adjusted life years (DALYs). The increasing prevalence of BD highlights the need for better diagnostic tools, particularly those involving genetic insights. Genetic association studies can play a crucial role in identifying variations linked to BD, shedding light on its genetic underpinnings and potential therapeutic targets. This study aimed to identify novel genetic variants associated with BD in the Taiwanese Han population and to elucidate their potential roles in disease pathogenesis. Genotyping was conducted using the Taiwan Precision Medicine Array (TPM Array) on 128 BD patients and 26,122 control subjects. Following quality control, 280,177 single nucleotide polymorphisms (SNPs) were analyzed via chi-square tests, and linkage disequilibrium (LD) analyses were employed to examine the associations among key SNPs. Eleven SNPs reached significance ( < 10), with the variant rs11156606 in the ABCD1 gene-implicated in fatty acid metabolism-emerging as a prominent finding. LD analysis revealed that rs11156606 is strongly linked with rs73640819, located in the 3' untranslated region, suggesting a regulatory role in gene expression. Additionally, rs3829533 in the MTHFSD gene was found to be in strong LD with the missense variants rs3751800 and rs3751801, indicating potential alterations in protein function. These findings enhance the genetic understanding of BD within a Taiwanese cohort by identifying novel risk-associated variants and support the potential for using these markers in early diagnosis and targeted therapeutic strategies.
近年来，双相情感障碍（BD）作为一种以严重发作性情绪波动为特征的多方面情绪障碍，已被证明会影响伤残调整生命年（DALYs）。BD患病率的上升凸显了对更好的诊断工具的需求，特别是那些涉及基因见解的工具。基因关联研究在识别与BD相关的变异、阐明其遗传基础和潜在治疗靶点方面可以发挥关键作用。本研究旨在识别台湾汉族人群中与BD相关的新基因变异，并阐明它们在疾病发病机制中的潜在作用。使用台湾精准医学阵列（TPM Array）对128例BD患者和26,122例对照受试者进行基因分型。经过质量控制后，通过卡方检验分析了280,177个单核苷酸多态性（SNP），并采用连锁不平衡（LD）分析来检查关键SNP之间的关联。11个SNP达到显著水平（<10），其中ABCD1基因中涉及脂肪酸代谢的变异rs11156606成为一个突出发现。LD分析显示，rs11156606与位于3'非翻译区的rs73640819紧密连锁，表明在基因表达中起调控作用。此外，发现MTHFSD基因中的rs3829533与错义变异rs3751800和rs3751801处于强LD状态，表明蛋白质功能可能发生改变。这些发现通过识别新的风险相关变异增强了对台湾人群中BD的遗传理解，并支持将这些标记物用于早期诊断和靶向治疗策略的潜力。
