Age-related macular degeneration: A high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease
Age-related macular degeneration: A high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease
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DOI：
10.1086/382786
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发表时间：
2004-03-01
影响因子：
9.8
通讯作者：
Swaroop, A
中科院分区：
文献类型：
--
作者：
Abecasis, GR;Yashar, BM;Swaroop, A
与年龄相关的黄斑变性（AMD）是一种影响视网膜中心区域的复杂多因素疾病。 AMD在临床上是异质的，导致地理萎缩（GA）和/或晚期脉络膜新生血管形成（CNV）。存在大量数据，以支持AMD的遗传倾向。最近的连锁研究提供了有利于几个AMD易感基因座的证据。我们进行了412对受影响的相对对的高分辨率（5-CM）基因组扫描，该对富含晚期疾病（GA和/或CNV）。使用两个不同的诊断标准进行非参数连锁分析，并根据GA或CNV表型将受影响的个体划分。我们的结果证明了在至少一项先前在染色体1q（Marshfield遗传图中的236-240 cm），5p（40-50 cm）和9q（111 cm）的区域中提出了联系的证据。用CNV对受影响亲戚的多点分析提供了染色体2p（10 cm）和22q（25 cm）的其他易感基因座的证据。在受限制组的274名患有AMD的受影响的成员中，未检测到最近发现的半囊蛋白-1染色体上半尿素1的GLN5345ARG变化，346例AMD患者和237例未受影响的对照。我们的结果巩固了几个AMD易感基因座的染色体位置，并与先前的报道一起，应促进寻找与疾病相关的序列变体。
Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the central region of the retina. AMD is clinically heterogeneous, leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at advanced stages. Considerable data exists in support of a genetic predisposition for AMD. Recent linkage studies have provided evidence in favor of several AMD susceptibility loci. We have performed a high-resolution (5-cM) genome scan of 412 affected relative pairs that were enriched for late-stage disease ( GA and/or CNV). Nonparametric linkage analysis was performed using two different diagnostic criteria and also by dividing the affected individuals according to GA or CNV phenotype. Our results demonstrate evidence of linkage in regions that were suggested in at least one previous study at chromosomes 1q ( 236 - 240 cM in the Marshfield genetic map), 5p ( 40 - 50 cM), and 9q ( 111 cM). Multipoint analysis of affected relatives with CNV provided evidence of additional susceptibility loci on chromosomes 2p ( 10 cM) and 22q ( 25 cM). A recently identified Gln5345Arg change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected members in the restricted group with AMD, 346 additional patients with AMD, and 237 unaffected controls. Our results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants.