Intraocular pressure(IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues fo...Intraocular pressure(IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance of P<9×10^(-7), and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance of P<5×10^(-8), including 4 previously reported loci: rs145063132(7 p21.2, ETV1/DGKB), rs548030386(7 q31.2, ST7 near CAV1/CAV2), rs7047871(9 p24.2, GLIS3), and rs2472494(9 q31.1, ABCA1/SLC44 A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes: PTCH2(rs7525308 in 1 p34.1), LRIF1/DRAM2(rs1282146 in 1 p13.3), COLEC11(rs201143466 in 2 p25.3),SPTBN1(rs4514918 in 2 p16.2), and CRK(rs11078446 in 17 p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.展开更多
Background:Neovascular age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)are sight-threatening maculopathies with both environmental and genetic risk factors.We have previously shown relat...Background:Neovascular age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)are sight-threatening maculopathies with both environmental and genetic risk factors.We have previously shown relative risks posed by genes of the complement pathways to neovascular AMD and PCV.Methods:In this study,we investigated the haplotype-tagging single nucleotide polymorphisms(SNPs)in the complement component 5(C5)gene in 708 unrelated Chinese individuals:200 neovascular AMD patients,233 PCV patients and 275 controls.Six tagging SNPs in C5 were genotyped.Univariate single SNP association analysis,haplotype-based association analysis and gene-gene interaction analysis between C5 and other AMD-associated genes were performed.Results:The results revealed none of the six tagging SNPs of the C5 gene had a significant association with neovascular AMD or PCV(P>0.05).We also found insignificant haplotype-based association,and no significant SNPSNP interaction between C5 and other genes(including C2-CFB-RDBP-SKIV2L,SERPING1,CETP,ABCG1,PGF,ANGPT2,CFH and HTRA1)for neovascular AMD and PCV.Conclusions:This study showed no statistical significance in the genetic association of C5 with neovascular AMD or PCV in a Hong Kong Chinese population.Further studies in large samples from different populations are warranted to elucidate the role of C5 in the genetic susceptibility of AMD and PCV.展开更多
基金supported by the National Precision Medicine Project (2016YFC0905200 and 2017YFC0907302)the National Natural Science Foundation of China (81430008, 81790643, 81300802, 81670895, 81670853, 81570888 and 81870683)+2 种基金the Department of Science and Technology of Sichuan Province, China (2014SZ0169, 2015SZ0052, 2014FZ0124, 2015JQO057, 2017JQ0024, 2016HH0072, 2013JY0195 and 2016JQ0026)High-level Talents Program of UESTC (Y03001023601021016)the Top-Notch Young Talents Program of China (Y.S.)
文摘Intraocular pressure(IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance of P<9×10^(-7), and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance of P<5×10^(-8), including 4 previously reported loci: rs145063132(7 p21.2, ETV1/DGKB), rs548030386(7 q31.2, ST7 near CAV1/CAV2), rs7047871(9 p24.2, GLIS3), and rs2472494(9 q31.1, ABCA1/SLC44 A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes: PTCH2(rs7525308 in 1 p34.1), LRIF1/DRAM2(rs1282146 in 1 p13.3), COLEC11(rs201143466 in 2 p25.3),SPTBN1(rs4514918 in 2 p16.2), and CRK(rs11078446 in 17 p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.
基金supported in part by the General Research Fund,Hong Kong(14120516[LJC])the Direct Grant of Chinese University of Hong Kong Medical Panel,Hong Kong(4054281[LJC])the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre,Hong Kong.
文摘Background:Neovascular age-related macular degeneration(AMD)and polypoidal choroidal vasculopathy(PCV)are sight-threatening maculopathies with both environmental and genetic risk factors.We have previously shown relative risks posed by genes of the complement pathways to neovascular AMD and PCV.Methods:In this study,we investigated the haplotype-tagging single nucleotide polymorphisms(SNPs)in the complement component 5(C5)gene in 708 unrelated Chinese individuals:200 neovascular AMD patients,233 PCV patients and 275 controls.Six tagging SNPs in C5 were genotyped.Univariate single SNP association analysis,haplotype-based association analysis and gene-gene interaction analysis between C5 and other AMD-associated genes were performed.Results:The results revealed none of the six tagging SNPs of the C5 gene had a significant association with neovascular AMD or PCV(P>0.05).We also found insignificant haplotype-based association,and no significant SNPSNP interaction between C5 and other genes(including C2-CFB-RDBP-SKIV2L,SERPING1,CETP,ABCG1,PGF,ANGPT2,CFH and HTRA1)for neovascular AMD and PCV.Conclusions:This study showed no statistical significance in the genetic association of C5 with neovascular AMD or PCV in a Hong Kong Chinese population.Further studies in large samples from different populations are warranted to elucidate the role of C5 in the genetic susceptibility of AMD and PCV.
