Contreras J, Hare E, Chavarría G, Raventós H
Centro de Investigación en Biología Celular y Molecular, Universidad de Costa Rica, Costa Rica.
Genetics and Genomics Research and Breeding Program Planning, Dog Genetics LLC., Sunnyside, NY, United States.
J Affect Disord. 2018 Jan 1;225:395-398. doi: 10.1016/j.jad.2017.08.023. Epub 2017 Aug 15.
Bipolar disorder type I (BPI) affects approximately 1% of the world population. Although genetic influences on bipolar disorder are well established, identification of genes that predispose to the illness has been difficult. Most genetic studies are based on categorical diagnosis. One strategy to overcome this obstacle is the use of quantitative endophenotypes, as has been done for other medical disorders.
We studied 619 individuals, 568 participants from 61 extended families and 51 unrelated healthy controls. The sample was 55% female and had a mean age of 43.25 (SD 13.90; range 18-78). Heritability and genetic correlation of the trait scale from the Anxiety State and Trait Inventory (STAI) was computed by using the general linear model (SOLAR package software).
we observed that anxiety trait meets the following criteria for an endophenotype of bipolar disorder type I (BPI): 1) association with BPI (individuals with BPI showed the highest trait score (F = 15.20 [5,24], p = 0.009), 2) state-independence confirmed after conducting a test-retest in 321 subjects, 3) co-segregation within families 4) heritability of 0.70 (SE: 0.060), p = 2.33 × 10 and 5) genetic correlation with BPI was 0.20, (SE = 0.17, p = 3.12 × 10).
Confounding factors such as comorbid disorders and pharmacological treatment could affect the clinical relationship between BPI and anxiety trait. Further research is needed to evaluate if anxiety traits are specially related to BPI in comparison with other traits such as anger, attention or response inhibition deficit, pathological impulsivity or low self-directedness.
Anxiety trait is a heritable phenotype that follows a normal distribution when measured not only in subjects with BPI but also in unrelated healthy controls. It could be used as an endophenotype in BPI for the identification of genomic regions with susceptibility genes for this disorder.
I型双相情感障碍（BPI）影响着全球约1%的人口。尽管双相情感障碍受遗传因素的影响已得到充分证实，但确定导致该疾病的基因却很困难。大多数基因研究基于分类诊断。克服这一障碍的一种策略是使用定量内表型，其他医学疾病的研究已采用此方法。
我们研究了619名个体，其中包括来自61个大家庭的568名参与者和51名无血缘关系的健康对照者。样本中女性占55%，平均年龄为43.25岁（标准差13.90；范围18 - 78岁）。使用一般线性模型（SOLAR软件包）计算焦虑状态与特质问卷（STAI）中特质量表的遗传度和遗传相关性。
我们观察到，焦虑特质符合I型双相情感障碍（BPI）内表型的以下标准：1）与BPI相关（BPI个体的特质得分最高（F = 15.20 [5,24]，p = 0.009）），2）在321名受试者中进行重测后证实状态独立性，3）在家族内共分离，4）遗传度为0.70（标准误：0.060），p = 2.33 × 10，5）与BPI的遗传相关性为0.20，（标准误 = 0.17，p = 3.12 × 10）。
共病障碍和药物治疗等混杂因素可能影响BPI与焦虑特质之间的临床关系。与愤怒、注意力或反应抑制缺陷、病理性冲动或低自我导向等其他特质相比，焦虑特质是否与BPI有特殊关联，还需要进一步研究评估。
焦虑特质是一种可遗传的表型，不仅在BPI患者中测量时呈正态分布，在无血缘关系的健康对照者中测量时也是如此。它可作为BPI的内表型，用于识别该疾病易感基因所在的基因组区域。
