Boomsma D I, Beem A L, van den Berg M, Dolan C V, Koopmans J R, Vink J M, de Geus E J, Slagboom P E
Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Twin Res. 2000 Dec;3(4):323-34. doi: 10.1375/136905200320565300.
In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic-epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression.
在一项针对荷兰青少年和青年双胞胎及其父母和兄弟姐妹的纵向研究中，通过问卷调查收集了有关抑郁、焦虑以及相关人格特质（如神经质）的数据。数据于1991年、1993年、1995年和1997年通过邮寄调查收集。该研究共纳入了来自3344个家庭的13717名个体。为了定位与焦虑和抑郁相关的数量性状基因座（QTL），利用调查数据选择了最具信息价值的家庭进行全基因组搜索。基于对焦虑、抑郁、神经质和躯体焦虑的遗传多变量分析，为每个个体计算了一个遗传因子得分。如果至少有两个兄弟姐妹（或异卵双胞胎）具有极端因子得分，则选择该家庭。所选样本中包括不一致（高 - 低）和一致（高 -高和低 - 低）的对子。一旦选择了一对极端的兄弟姐妹，就会要求所有至少有一次返回问卷小册子的家庭成员（所选对子的父母和其他兄弟姐妹）提供DNA样本。总共接触了来自563个家庭的2724名个体（1007名父母和1717名后代），479个家庭的1975名个体（643名患者和1332名后代）通过返回口腔拭子用于DNA分离而表示同意。所选家庭的所有后代都被要求参加一次精神病学访谈以及对心血管参数和皮质醇的24小时动态评估。该访谈由世界卫生组织综合国际诊断访谈组成，并对1253名后代进行了访谈。在本文中，我们描述了对焦虑、躯体焦虑、神经质和抑郁调查数据的遗传流行病学分析。我们详细说明了如何利用这些数据选择用于QTL研究的家庭，并讨论了可能有助于阐明从基因到焦虑抑郁的分子途径的策略。
