Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.
Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.
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DOI：
10.1371/journal.pone.0018044
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发表时间：
2011-04-20
期刊：
影响因子：
3.7
通讯作者：
Afshari NA
中科院分区：
文献类型：
--
作者：
Li YJ;Minear MA;Rimmler J;Zhao B;Balajonda E;Hauser MA;Allingham RR;Eghrari AO;Riazuddin SA;Katsanis N;Gottsch JD;Gregory SG;Klintworth GK;Afshari NA
富克斯角膜内皮营养不良（FECD）是一种常见的迟发性角膜内皮疾病。虽然通过研究以常染色体显性遗传方式传播表型的大家族在理解FECD的遗传基础方面取得了进展，但最近报道的全基因组关联研究在18号染色体上靠近TCF 4的一个位点确定了共同的等位基因，该位点赋予FECD的易感性。在这里，我们报告了我们使用迄今为止最大的FECD数据集（450例FECD病例和340例正常对照）进行的TCF 4独立验证研究的结果。对三种遗传模型进行了以性别为协变量的逻辑回归：显性（DOM）、加性（ADD）和隐性（REC）。我们发现与Baratz等人报道的靶标记rs613872显著相关。（2010），对于所有三个遗传模型（DOM：P = 9.33×10−35; ADD：P = 7.48×10−30; REC：P = 5.27×10−6）。 为了加强关联研究，我们还进行了全基因组连锁扫描64个多重家庭，主要由受影响的兄弟姐妹对（ASP），使用参数和非参数两点和多点分析。最显著的连锁区域位于第18号染色体69.94 ~ 85.29cM之间，在DOM模型下，多点HLOD峰值为2.5，位于rs 1145315（75.58cM），定位在rs613872附近1.5Mb。 总之，我们的研究通过关联和连锁研究提供了支持内含子TCF 4单核苷酸多态性rs613872在晚发型FECD中作用的证据。
Fuchs endothelial corneal dystrophy (FECD) is a common, late-onset disorder of the corneal endothelium. Although progress has been made in understanding the genetic basis of FECD by studying large families in which the phenotype is transmitted in an autosomal dominant fashion, a recently reported genome-wide association study identified common alleles at a locus on chromosome 18 near TCF4 which confer susceptibility to FECD. Here, we report the findings of our independent validation study for TCF4 using the largest FECD dataset to date (450 FECD cases and 340 normal controls). Logistic regression with sex as a covariate was performed for three genetic models: dominant (DOM), additive (ADD), and recessive (REC). We found significant association with rs613872, the target marker reported by Baratz et al.(2010), for all three genetic models (DOM: P = 9.33×10−35; ADD: P = 7.48×10−30; REC: P = 5.27×10−6). To strengthen the association study, we also conducted a genome-wide linkage scan on 64 multiplex families, composed primarily of affected sibling pairs (ASPs), using both parametric and non-parametric two-point and multipoint analyses. The most significant linkage region localizes to chromosome 18 from 69.94cM to 85.29cM, with a peak multipoint HLOD = 2.5 at rs1145315 (75.58cM) under the DOM model, mapping 1.5 Mb proximal to rs613872. In summary, our study presents evidence to support the role of the intronic TCF4 single nucleotide polymorphism rs613872 in late-onset FECD through both association and linkage studies.
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DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
DOI：
10.1016/s0896-1549(01)00016-5
发表时间：
2002-03-01
期刊：
Ophthalmology clinics of North America
影响因子：
--
作者：
Borboli, Sheila;Colby, Kathryn
通讯作者：
Colby, Kathryn
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
14.9
作者：
Bult CJ;Blake JA;Smith CL;Kadin JA;Richardson JE;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
影响因子：
4.4
作者：
Aldave, Anthony J.;Rayner, Sylvia A.;Yellore, Vivek S.
通讯作者：
Yellore, Vivek S.