2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/648133摘要：躁鬱症及重鬱症是重要公共衛生議題之一。此兩種嚴重情感性精神疾病不但造成病人重要社會功能的損害，其疾病病程也常是慢性的，伴隨一再復發的躁症或是鬱症發作。情感性精神疾病的復發率高，然病人病識感普遍不佳，就診治療率也偏低，造成極大的個人以及社會之疾病負擔。過去的研究顯示躁鬱症及重鬱症有家族聚集現象，以及中至高程度的遺傳度，尤其是躁鬱症其遺傳度高達八成。因而瞭解遺傳因子對於躁鬱症及重鬱症的影響相當重要，不僅貢獻於嚴重情感性精神疾病的病因探討，也是未來協助改善藥物治療療效的基礎。遺傳研究的進行，容易受到不同人口種族的影響，也有其地域特殊性。本研究計畫的主要目的在於識別出華人中影響情感性精神疾病的重要遺傳因子。在第一階段，本研究將採用混合式(DNA pooling)全基因體掃瞄的策略，進行無先驗遺傳基因假設的病例對照遺傳相關分析。選出在此一階段相對重要的遺傳標記，進入第二階段個人式的基因標記鑑定，以找出與情感性疾患相關的基因。經此兩階段混合式全基因體掃瞄後達顯著的基因，則藉由另一以家族研究設計為主的獨立樣本，看是否能複製此兩階段遺傳研究的結果。我們將持續進行躁鬱症及重鬱症指標個案的收案工作，藉由訪談詳細測量表現型及其臨床症狀特徵。利用現今進步的基因型偵測技術，進行一連串遺傳相關分析，以找出在情感性疾患中扮演重要角色的基因與標記。透過上述的研究目標，本研究計畫的結果預期能從臨床特徵以及基因體特徵兩方面，更加瞭解躁鬱症及重鬱症的可能致病病因。以研究的實證資料結果，期提供未來診斷、治療、臨床照護上的參考。<br> Abstract: Bipolar disorder (BPD) and major depressive disorder (MDD) are two main severe mood disorders characterized by recurrent episodes of mania/depression and the disease course is usually chronic with extended functional impairment. BPD and MDD together cause great burden of disease globally and the cost on individual and society is enormous due to high recurrence rate and low treatment proportion among affected people. The two disorders exhibited familial aggregation with moderate to high heritability. Searching genes in ethnically more homogeneous group is critical for understanding the genetic background for mood disorders, which forms important groundwork for assisting to identify treatment target in the future. The goal of the present study is to identify genetic key players in mood disorders in Chinese. The present study proposes to conduct a hypothesis-free case-control genome-wide association study (GWAS) using DNA pooling strategy at the first stage. A set of top-ranked markers will be selected for individual genotyping at the second stage. Significant results from the cost-effective two-stage DNA pooling GWAS will then be examined in an independent family-based sample for replication. We first continue the ongoing data collection efforts with detailed phenotypic measures. Secondly, we employ a series of genotyping strategies and genetic association analyses to identify susceptible genes in mood disorders. We anticipate to contributing on understanding the etiology of mood disorders from both clinical and genomic points of view. Study results may point a way in the future to improve diagnostic reliability and quality of treatment and clinical care.