A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.
A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.
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一项多种族全基因组关联研究暗示圆锥角膜中胶原基质完整性和细胞分化途径。
DOI：
10.1038/s42003-021-01784-0
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发表时间：
2021-03-01
影响因子：
5.9
通讯作者：
Hysi PG
中科院分区：
文献类型：
--
作者：
Hardcastle AJ;Liskova P;Bykhovskaya Y;McComish BJ;Davidson AE;Inglehearn CF;Li X;Choquet H;Habeeb M;Lucas SEM;Sahebjada S;Pontikos N;Lopez KER;Khawaja AP;Ali M;Dudakova L;Skalicka P;Van Dooren BTH;Geerards AJM;Haudum CW;Faro VL;Tenen A;Simcoe MJ;Patasova K;Yarrand D;Yin J;Siddiqui S;Rice A;Farraj LA;Chen YI;Rahi JS;Krauss RM;Theusch E;Charlesworth JC;Szczotka-Flynn L;Toomes C;Meester-Smoor MA;Richardson AJ;Mitchell PA;Taylor KD;Melles RB;Aldave AJ;Mills RA;Cao K;Chan E;Daniell MD;Wang JJ;Rotter JI;Hewitt AW;MacGregor S;Klaver CCW;Ramdas WD;Craig JE;Iyengar SK;O'Brart D;Jorgenson E;Baird PN;Rabinowitz YS;Burdon KP;Hammond CJ;Tuft SJ;Hysi PG
圆锥角膜的特征是角膜硬度降低，变形和局灶性变薄，导致视力模糊，然而，其发病机制尚不清楚。它可导致儿童和年轻人严重的视力发病率，是全球角膜移植的常见适应症。在这里，我们报告了第一个大规模的圆锥角膜全基因组关联研究，包括4，669例病例和116，547例对照。我们已经确定了与36个基因组位点的显着关联，这是第一次，涉及角膜胶原基质完整性和细胞分化途径作为主要致病机制的失调。结果还表明多效性，与其他角膜疾病，如富克斯角膜内皮营养不良共享的一些疾病机制。与圆锥角膜相关的常见变异解释了12.5%的遗传变异，这显示了未来开发诊断测试以检测疾病易感性的潜力。Alison Hardcastle等人报告了圆锥角膜的全基因组荟萃分析，圆锥角膜是一种影响角膜的疾病，会导致视力模糊，并经常导致失明。他们确定了36个与圆锥角膜相关的基因组区域，其中31个是新的，并表明这些区域中的基因涉及涉及胶原基质完整性和细胞分化的遗传途径。
Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease. Alison Hardcastle et al. report a genome-wide meta-analysis of keratoconus, a condition affecting the cornea that causes blurred vision and often leads to blindness. They identify 36 genomic regions associated with keratoconus, 31 of which are novel, and show that the genes in these regions implicate genetic pathways involved in collagen matrix integrity and cell differentiation.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
1.7
作者：
Bohac, Maja;Koncarevic, Mateja;Patel, Sudi
通讯作者：
Patel, Sudi
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ