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Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations

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机构: [1]Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore [2]Duke NUS Grad Med Sch, Ctr Quantitat Med, Singapore, Singapore [3]ASTAR, Genome Inst Singapore, Singapore, Singapore [4]NUS GIS Ctr Mol Epidemiol, Singapore, Singapore [5]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore 117595, Singapore [6]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore [7]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore [8]Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing, Peoples R China [9]Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA [10]Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA [11]Heidelberg Univ, Dept Ophthalmol, Med Fac Mannheim, Heidelberg, Germany [12]Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia
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Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent. We have followed up on all suggestive signals of association with CCT (P < 10(-4)) from the previously reported meta-analysis comprising Indians and Malays in a sample of Chinese individuals (n = 2681). In the combined sample (n 5 7711), strong evidence of association was observed at four novel loci: IBTK on chromosome 6q14.1; CHSY1 on chromosome 15q26.3; and intergenic regions on chromosomes 7q11.2 and 9p23 (8.01 x 10(-11) < lambda(GC) corrected P-meta < 8.72 x 10(-8)). These four new loci explain an additional 4.3% of the total CCT variance across the sample cohorts over and above that of previously identified loci. We also extend on a previous finding at a fifth locus (AKAP13) where a new single-nucleotide polymorphism (rs1821481, P-meta = 9.99 x 10(-9)) was found to be significantly more informative compared with the previously reported rs6496932 (P-meta < 3.64 x 10(-5)). Performing association analysis in Asians may lead to the discovery of ethnic-specific genes that control CCT, offering further mechanistic insights into the regulation of CCT. In addition, it may also provide several candidate genes for interrogation for POAG, keratoconus and possible racial/ethnic variations.

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出版当年[2011]版:
大类 | 2 区 生物
小类 | 2 区 生化与分子生物学 2 区 遗传学
最新[2023]版:
大类 | 2 区 生物学
小类 | 3 区 生化与分子生物学 3 区 遗传学
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出版当年[2010]版:
Q1 GENETICS & HEREDITY Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q2 GENETICS & HEREDITY Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2010版] 出版当年五年平均 出版前一年[2009版] 出版后一年[2011版]

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第一作者机构: [1]Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore [2]Duke NUS Grad Med Sch, Ctr Quantitat Med, Singapore, Singapore
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通讯机构: [1]Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore [7]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore [*1]Singapore Natl Eye Ctr, Singapore Eye Res Inst, 11 3rd Hosp Ave, Singapore 168751, Singapore
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