Infectious Diseases, Genome Institute of Singapore, A*STAR, Singapore.
Hum Mol Genet. 2011 May 1;20(9):1864-72. doi: 10.1093/hmg/ddr060. Epub 2011 Feb 9.
Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n = 2132 of Indian and n = 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n = 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, per-allele change in optic disc area = 0.051 mm(2); P(meta) = 2.73×10(-12)) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, P(meta) = 7.57×10(-17)) and ATOH7 (lead SNP rs7916697, P(meta) = 2.00 × 10(-15)) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.
视神经损伤(例如青光眼)会对视力产生不良且往往是不可逆转的影响。早期的研究表明,视神经头的大小可能受遗传因素的控制。我们对 4445 名新加坡人(分别为印度裔 2132 名和马来裔 2313 名)进行了全基因组关联研究(GWAS),使用最广泛报道的视盘特征参数(视盘面积),在荷兰鹿特丹(n = 9326 名白种人)进行了复制。我们在 22q13.1 染色体上确定了一个新的位置,CARD10,它在新加坡两个队列以及鹿特丹研究(RS)中与视盘面积强烈相关(rs9607469,视盘面积每等位基因变化=0.051mm2;P(meta)=2.73×10(-12)),并证实了 CDC7/TGFBR3(先导单核苷酸多态性(SNP)rs1192415,P(meta)=7.57×10(-17))和 ATOH7(先导 SNP rs7916697,P(meta)=2.00×10(-15))与亚洲人的视盘面积之间的关联。这是第一项基于亚洲人的视盘面积全基因组关联研究,确定了视盘面积的一个新位置,但也证实了在白种人中发现的结果,表明存在适用于不同种族视盘大小的一般遗传决定因素。
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