Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis

详细信息    查看全文

• 作者：Abigail Woodroffe ; Charles M. Krafchak ; Nobuo Fuse ; Paul R. Lichter ; Sayoko E. Moroi ; Robert Schertzer ; Catherine A. Downs ; William L. Duren ; Michael Boehnke and Julia E. Richards
• 关键词：ordered subset analysis ; linkage mapping ; open-angle glaucoma ; juvenile glaucoma ; normal tension glaucoma ; genetic heterogeneity ; complex traits ; age at diagnosis
• 刊名：Experimental Eye Research
• 出版年：2006
• 出版时间：June 2006
• 年：2006
• 卷：82
• 期：6
• 页码：1068-1074
• 全文大小：164 K

文摘

Open angle glaucoma (OAG) is a complex disorder with varying etiologies due to multiple genes and environmental effects. This genetic heterogeneity can confound efforts to map loci. Increased homogeneity in a sample can be achieved using either ordered subset analysis (OSA) which groups families, or individual OSA (IOSA), which groups individuals based on disease related covariates. Recently, GLC1I was mapped to 15q11–13 in families with early adult onset of OAG. We tested for linkage to GLC1I in an independent sample of 167 individuals in 25 multiplex OAG families of European descent. We carried out nonparametric linkage analysis on the complete set of 25 families and obtained a maximum LOD score of 1.00 at 9.0 cM. Using mean age at diagnosis (AAD) across the affected individuals within each family to order the families as a proxy for age at onset, we found a maximum OSA LOD score of 2.09 (p