Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
Eur J Hum Genet. 2010 Apr;18(4):496-501. doi: 10.1038/ejhg.2009.185. Epub 2009 Oct 21.
About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes.
大约 40%的年龄相关性黄斑变性 (AMD) 的遗传变异可以用五个常见的单核苷酸多态性 (SNP) 的常见变异来解释。我们评估了这些已知变体在一组受 AMD 严重影响的家族中解释 AMD 聚类的程度。我们试图确定在受 AMD 严重影响的家族中，五个变体的实际风险等位基因数量是否与预期数量相匹配。我们使用了 322 个 AMD 家族的数据，使用模拟策略生成了家族的对照组，并确定了在给定观察到的疾病密度的情况下，已知 AMD 风险基因座的家族的遗传特征是否与观察到的遗传特征不同。总体而言，这五个 SNP 在家族中的基因型负荷与模拟预测的基因型负荷没有显著差异。然而，对于一部分受 AMD 严重影响的家族，家族中的平均基因型负荷明显低于从模拟中确定的预期负荷。鉴于这些受 AMD 严重影响的家族可能携带罕见的、更具穿透力的 AMD 变体，针对这些家族的连锁分析和重测序可能是发现其他受影响基因的有效方法。
