Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Transl Psychiatry. 2012 Sep 25;2(9):e165. doi: 10.1038/tp.2012.81.
Research suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry. Rs9875793, which is located in an intergenic region of 3q26.1 and in the vicinity of the solute carrier family 2 (facilitated glucose transporter), member 2 gene (SLC2A2), was significantly associated with the factor analysis-derived dimension 'negative mood delusions' (n=927; P=4.65 × 10(-8), odds ratio (OR)=2.66). This dimension was comprised of the symptoms delusions of poverty, delusions of guilt and nihilistic delusions. In case-control analyses, significant association with the G allele of rs9875793 was only observed in the subgroup of BD patients who displayed symptoms of 'negative mood delusions' (allelic χ(2) model: P(G)=0.0001, OR=1.92; item present, n=89). Further support for the hypothesis that rs9875793 is associated with BD in patients displaying 'negative mood delusions' symptom, such as delusions of guilt, was obtained from an European American sample (GAIN/TGEN), which included 1247 BD patients and 1434 controls (P(EA)=0.028, OR=1.27).
研究表明，临床症状维度可能比标准诊断模型更有助于阐明双相情感障碍（BD）的遗传学。迄今为止，尚无研究将这一概念应用于全基因组关联研究（GWAS）的数据。我们对 927 名具有德国血统的临床特征明确的 BD 患者进行了因子维度的 GWAS。位于 3q26.1 基因间区和溶质载体家族 2（易化葡萄糖转运体）成员 2 基因（SLC2A2）附近的 Rs9875793 与因子分析衍生的维度“负性情绪妄想”显著相关（n=927；P=4.65×10（-8），比值比（OR）=2.66）。这个维度包括妄想贫困、罪恶妄想和虚无妄想的症状。在病例对照分析中，仅在显示“负性情绪妄想”症状的 BD 患者亚组中观察到 rs9875793 的 G 等位基因与该维度显著相关（等位基因 χ(2)模型：P(G)=0.0001，OR=1.92；项目存在，n=89）。GAIN/TGEN 包含 1247 名 BD 患者和 1434 名对照，进一步支持了 rs9875793 与显示负性情绪妄想症状（如罪恶妄想）的 BD 患者相关的假设（GAIN/TGEN）（P(EA)=0.028，OR=1.27）。
