Saunders Erika H, Scott Laura J, McInnis Melvin G, Burmeister Margit
University of Michigan Depression Center, Ann Arbor, Michigan 48109, USA.
Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):18-26. doi: 10.1002/ajmg.b.30558.
Bipolar-related subphenotypes that cluster within families may help identify subsets of patients that are more genetically homogeneous. Environmental or assessment factors that segregate by family may influence estimates of familiality. We aimed to determine familiality of subphenotypes of bipolar disorder (BP), accounting for effects of age, sex, diagnosis, and site/wave of ascertainment. We studied 589 sibships with 1416 siblings affected with bipolar I (BPI), schizoaffective disorder, bipolar type (SAB), bipolar II (BPII), or recurrent unipolar depression (RUDD). Sibships were from families with > or =2 BPI cases collected by the NIMH Bipolar Genetics Initiative (NIMHBGI). Rapid cycling showed the strongest evidence for familiality [odds ratio (OR) (95%CI) = 2.02 (1.43, 2.85), P = 6.0 x 10(-5)] in a model including age, sex, diagnosis, and site/wave of ascertainment. Additional significantly familial traits were comorbid alcohol abuse/dependence (P = 2 x 10(-4)) and comorbid panic disorder (P = 8 x 10(-3)), as well as psychosis, suicidal thoughts, and rapid mood switching (P = 6 x 10(-3) - 0.03). Omission of the effect of site/wave of ascertainment from the model inflated the significance level of the apparent familial association of almost all subphenotypes from one to four orders of magnitude. We have found evidence of familiality for subphenotypes of BP. In multicenter samples, familiality may be overestimated if variability in diagnosis of subphenotypes between site/wave of ascertainment is not considered.
在家族内聚集的双相情感障碍相关亚表型可能有助于识别基因上更具同质性的患者亚组。按家族分类的环境或评估因素可能会影响家族性估计。我们旨在确定双相情感障碍（BP）亚表型的家族性，同时考虑年龄、性别、诊断以及确诊地点/批次的影响。我们研究了589个同胞兄弟姐妹家庭，其中1416名兄弟姐妹患有双相I型障碍（BPI）、分裂情感性障碍（双相型，SAB）、双相II型障碍（BPII）或复发性单相抑郁症（RUDD）。这些同胞兄弟姐妹家庭来自美国国立精神卫生研究所双相情感障碍遗传学倡议项目（NIMHBGI）收集的有≥2例BPI病例的家庭。在一个包含年龄、性别、诊断以及确诊地点/批次的模型中，快速循环显示出最强的家族性证据[优势比（OR）（95%置信区间）= 2.02（1.43，2.85），P = 6.0×10⁻⁵]。其他具有显著家族性的特征包括共病酒精滥用/依赖（P = 2×10⁻⁴）、共病惊恐障碍（P = 8×10⁻³），以及精神病性症状、自杀观念和快速情绪转换（P = 6×10⁻³ - 0.03）。在模型中忽略确诊地点/批次的影响会使几乎所有亚表型的明显家族关联的显著性水平从1个数量级膨胀到4个数量级。我们发现了BP亚表型存在家族性的证据。在多中心样本中，如果不考虑确诊地点/批次之间亚表型诊断的变异性，家族性可能会被高估。
