Li Yi-Ju, Goh Liang, Khor Chiea-Chuen, Fan Qiao, Yu Miao, Han Siyu, Sim Xueling, Ong Rick Twee-Hee, Wong Tien-Yin, Vithana Eranga Nishanthie, Yap Eric, Nakanishi Hideo, Matsuda Fumihiko, Ohno-Matsui Kyoko, Yoshimura Nagahisa, Seielstad Mark, Tai E-Shyong, Young Terri L, Saw Seang-Mei
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.
Ophthalmology. 2011 Feb;118(2):368-75. doi: 10.1016/j.ophtha.2010.06.016. Epub 2010 Nov 20.
To determine susceptibility genes for high myopia in Singaporean Chinese.
A meta-analysis of 2 genome-wide association (GWA) datasets in Chinese and a follow-up replication cohort in Japanese.
Two independent datasets of Singaporean Chinese individuals aged 10 to 12 years (Singapore Cohort Study of the Risk factors for Myopia [SCORM]: cases = 65, controls = 238) and more than 21 years (Singapore Prospective Study Program [SP2]: cases = 222, controls = 435) for GWA studies, and a Japanese dataset aged more than 20 years (cases = 959, controls = 2128) for replication.
Genomic DNA samples from SCORM and SP2 were genotyped using various Illumina Beadarray platforms (>HumanHap 500). Single-locus association tests were conducted for each dataset with meta-analysis using pooled z-scores. The top-ranked genetic markers were examined for replication in the Japanese dataset. Fisher P was calculated for the combined analysis of all 3 cohorts.
High myopia, defined by spherical equivalent (SE) ≤ -6.00 diopters (D); controls defined by SE between -0.50 and +1.00 D.
Two SNPs (rs12716080 and rs6885224) in the gene CTNND2 on chromosome 5p15 ranked top in the meta-analysis of our Chinese datasets (meta P = 1.14 × 10(-5) and meta P = 1.51 × 10(-5), respectively) with strong supporting evidence in each individual dataset analysis (max P = 1.85 × 10(-4) in SCORM: max P = 8.8 × 10(-3) in SP2). Evidence of replication was observed in the Japanese dataset for rs6885224 (P = 0.035, meta P of 3 datasets: 7.84 × 10(-6)).
This study identified a strong association of CTNND2 for high myopia in Asian datasets. The CTNND2 gene maps to a known high myopia linkage region on chromosome 5p15.
确定新加坡华裔高度近视的易感基因。
对两个中国全基因组关联（GWA）数据集进行荟萃分析，并在日本进行后续重复队列研究。
两个独立的新加坡华裔个体数据集用于GWA研究，一个是10至12岁的个体（新加坡近视危险因素队列研究[SCORM]：病例=65，对照=238），另一个是21岁以上的个体（新加坡前瞻性研究计划[SP2]：病例=222，对照=435）；还有一个20岁以上的日本数据集（病例=959，对照=2128）用于重复研究。
使用各种Illumina Beadarray平台（>HumanHap 500）对来自SCORM和SP2的基因组DNA样本进行基因分型。对每个数据集进行单基因座关联测试，并使用合并的z分数进行荟萃分析。在日本数据集中检查排名靠前的遗传标记是否可重复。计算所有3个队列联合分析的Fisher P值。
高度近视定义为等效球镜（SE）≤ -6.00屈光度（D）；对照定义为SE在-0.50至+1.00 D之间。
在5号染色体p15上的CTNND2基因中的两个单核苷酸多态性（SNP，rs12716080和rs6885224）在我们中国数据集的荟萃分析中排名靠前（荟萃P值分别为1.14×10⁻⁵和1.51×10⁻⁵），在每个单独数据集分析中都有有力的支持证据（SCORM中最大P值=1.85×10⁻⁴；SP2中最大P值=8.8×10⁻³）。在日本数据集中观察到rs6885224的重复证据（P = 0.035，3个数据集的荟萃P值：7.84×10⁻⁶）。
本研究在亚洲数据集中确定了CTNND2与高度近视之间的强关联。CTNND2基因定位于5号染色体p15上一个已知的高度近视连锁区域。
