Assink Jacqueline J M, Klaver Caroline C W, Houwing-Duistermaat Jeanine J, Wolfs Roger C W, van Duijn Cornelia M, Hofman Albert, de Jong Paulus T V M
Department of Ophthalmogenetics, The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands.
Ophthalmology. 2005 Mar;112(3):482-7. doi: 10.1016/j.ophtha.2004.10.035.
To assess the extent of heterogeneity of the genetic risk of age-related macular disease (AMD) among families.
Case-controlled population-based familial aggregation study.
Participants comprised 190 first-degree relatives of 65 case probands and 347 relatives of 100 control probands. All probands had been identified from the baseline phase of the Rotterdam Study in The Netherlands.
A family score was computed for each family based on the presence and type of macular disease, the expected risk of disease, and the number, extent of kinship, and age of all family members.
Presence and stage of AMD as diagnosed on fundus photographs, family score, and logistic regression coefficient.
The family score of case families showed a peak of approximately 0 with a skewed tail (14% of families) of higher than expected risks of disease toward a maximum of 2.9. The family score of control families centered on 0, apart from 1 outlier. The risk of AMD increased significantly with higher family scores (beta = 1.34; P<0.001).
The heterogeneity of genetic risk among AMD families is considerable, and the proportion of high-risk families is relatively small. The family score method is relevant for genetic counseling as well as for implementation in studies of genetic dissection of AMD.
评估年龄相关性黄斑病变（AMD）家庭中遗传风险的异质性程度。
基于人群的病例对照家族聚集性研究。
参与者包括65例病例先证者的190名一级亲属和100名对照先证者的347名亲属。所有先证者均来自荷兰鹿特丹研究的基线阶段。
根据黄斑病变的存在和类型、疾病的预期风险以及所有家庭成员的数量、亲属关系程度和年龄，为每个家庭计算家族得分。
眼底照片诊断的AMD的存在和分期、家族得分以及逻辑回归系数。
病例家庭的家族得分显示峰值约为0，尾部呈偏态分布（14%的家庭），疾病风险高于预期，最高可达2.9。对照家庭的家族得分以0为中心，有1个异常值除外。AMD风险随着家族得分升高而显著增加（β = 1.34；P<0.001）。
AMD家庭中遗传风险的异质性相当大，高危家庭的比例相对较小。家族得分法对于遗传咨询以及AMD基因剖析研究的实施都具有重要意义。
