A genetic contribution to intraocular pressure: The Beaver Dam Eye Study
A genetic contribution to intraocular pressure: The Beaver Dam Eye Study
复制标题
DOI：
10.1167/iovs.04-0729
复制
发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Klein, BEK
中科院分区：
文献类型：
--
作者：
Duggal, P;Klein, AP;Klein, BEK
目的。为了调查遗传对眼压 (IOP) 的潜在影响，我们对通过基于人群的队列 Beaver Dam 眼科研究 (BDES) 确定的 620 个扩展谱系中的 2337 名个体进行了复杂的分离分析。 IOP 是原发性开角型青光眼 (POAG) 的主要危险因素，而 POAG 是全世界失明的主要原因。方法。分离分析是一种分析方法，提供支持主要基因或多基因参与特定表型的统计证据。对所有参与者进行了详细的病史和眼科检查。在调整协变量后，两只眼睛的较高眼压测量值被用作连续特征。对 218 对兄弟姐妹进行了全基因组扫描 (GWS)，使用受影响的兄弟姐妹对连锁分析。 结果。在此分离分析中，考虑到未测量的主要环境影响加上多基因/多因素影响的模型提供了最佳拟合，并且是最简约的模型。孟德尔单基因模型缺乏足够的拟合度，这与多因素遗传模型是一致的，多因素遗传模型可能包括导致眼压的多个基因和环境因素。 GWS 的结果产生了两个新的位点，作为 6 号染色体（P = 0.008）和 13 号染色体（P = 0.0007）上 IOP 的潜在连锁区域。这些区域之前都没有在 POAG 的 GWS 中被识别过。结论。 IOP 的分离和家族相关性分析表明存在受环境影响的多遗传因素。试点连锁研究通过鉴定两个新的遗传位点进一步证实了 IOP 的异质性。
PURPOSE. To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open-angle glaucoma (POAG) a leading cause of blindness worldwide.METHODS. Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. A genome-wide scan (GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs.RESULTS. In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/ multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single-gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P = 0.008) and 13 (P = 0.0007). Neither of these regions has previously been identified in GWS of POAG.CONCLUSIONS. The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further confirms the heterogeneity of IOP with the identification of two novel genetic loci.