SNPs significantly associated with ACD.

Anterior chamber depth (ACD) is a quantitative trait associated with primary angle closure glaucoma (PACG). Although ACD is highly heritable, known genetic variations explain a small fraction of the phenotypic variability. The purpose of this study was to identify additional ACD-influencing loci using strains of mice. Cohorts of 86 N2 and 111 F2 mice were generated from crosses between recombinant inbred BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical coherence tomography, mice were phenotyped at 10–12 weeks of age, genotyped based on 93 genome-wide SNPs, and subjected to quantitative trait locus (QTL) analysis. In an analysis of ACD among all mice, six loci passed the significance threshold of p = 0.05 and persisted after multiple regression analysis. These were on chromosomes 6, 7, 11, 12, 15 and 17 (named Acdq6, Acdq7, Acdq11, Acdq12, Acdq15, and Acdq17, respectively). Our findings demonstrate a quantitative multi-genic pattern of ACD inheritance in mice and identify six previously unrecognized ACD-influencing loci. We have taken a unique approach to studying the anterior chamber depth phenotype by using mice as genetic tool to examine this continuously distributed trait.

前房深度（Anterior chamber depth, ACD）是与原发性闭角型青光眼（Primary angle closure glaucoma, PACG）相关的数量性状。尽管ACD具有高度可遗传性，但已发现的遗传变异仅能解释小部分表型变异。本研究旨在通过小鼠品系鉴定额外的ACD影响位点。研究通过重组近交系BXD24/TyJ与野生来源CAST/EiJ小鼠杂交，构建了包含86只N2代及111只F2代小鼠的实验队列。于小鼠10至12周龄时采用前房光学相干断层扫描（anterior chamber optical coherence tomography）完成表型分型，基于93个全基因组单核苷酸多态性（SNPs）进行基因分型，并开展数量性状位点（quantitative trait locus, QTL）分析。对所有小鼠的ACD进行关联分析后，共6个位点达到p=0.05的显著性阈值，且经多元回归分析（multiple regression analysis）后仍保持显著关联，这些位点分别位于6、7、11、12、15及17号染色体，依次命名为Acdq6、Acdq7、Acdq11、Acdq12、Acdq15与Acdq17。本研究结果揭示了小鼠ACD遗传的多基因数量性状模式，并鉴定出6个此前未被报道的ACD影响位点。本研究采用了一种独特的研究策略：以小鼠作为遗传工具，探究这一连续分布的表型性状。