Croes Esther A, El Galta Rachid, Houwing-Duistermaat Jeanine J, Ferdinand Robert F, López León Sandra, Rademaker Tessa A M, Dekker Marieke C J, Oostra Ben A, Verhulst Frank, Van Duijn Cornelia M
Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Eur J Epidemiol. 2005;20(9):789-94. doi: 10.1007/s10654-005-0366-7.
We address the use of two informants in genetic studies and whether familial aggregation is similar for the three phenotypic subtypes of ADHD. Lifetime ADHD was diagnosed in a Dutch isolated population using parents and teachers as informants, creating two subgroups (one or two informants), then further divided into three phenotypic categories (inattentive, hyperactive/impulsive, combined). Genealogy was collected for all patients. Mean kinship coefficients for the subgroups were calculated. Fifteen of 26 children were linked to a common ancestor within 10 generations. The mean kinship coefficient of patients confirmed by two informants was significantly higher than in patients only scored positive by one informant (p = 0.03). All patients of the inattentive subtype were connected to a common ancestor, which was significantly higher (p = 0.03) than expected. Eighty-one percent of these patients derive of consanguineous marriages, also higher than expected. This means that recessive mutations may be involved in the inattentive subtype. These patients were more closely related than those with the other phenotypes (p<0.01). Our data suggests that using two informants in diagnosing ADHD helps identify a phenotype with a strong genetic component. The inattentive phenotype showed strong familial clustering and evidence of a recessive origin.
我们探讨了在基因研究中使用两名信息提供者的情况，以及注意缺陷多动障碍（ADHD）三种表型亚型的家族聚集性是否相似。在一个荷兰隔离人群中，以父母和教师作为信息提供者来诊断终生ADHD，从而创建了两个亚组（一名或两名信息提供者），然后进一步分为三种表型类别（注意力不集中型、多动/冲动型、混合型）。收集了所有患者的家谱。计算了各亚组的平均亲属系数。26名儿童中有15名在10代内与一位共同祖先有血缘关系。经两名信息提供者确诊的患者的平均亲属系数显著高于仅由一名信息提供者评定为阳性的患者（p = 0.03）。所有注意力不集中型亚型的患者都与一位共同祖先有血缘关系，这一比例显著高于预期（p = 0.03）。这些患者中有81%来自近亲婚姻，也高于预期。这意味着隐性突变可能与注意力不集中型亚型有关。这些患者之间的亲缘关系比其他表型的患者更密切（p<0.01）。我们的数据表明，在诊断ADHD时使用两名信息提供者有助于识别具有强大遗传成分的表型。注意力不集中型表型显示出强烈的家族聚集性以及隐性起源的证据。
