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https://doi.org/10.1038/s41467-018-03646-6
| Title: | Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases | Authors: | Iglesias, A.I Mishra, A Vitart, V etc. |
Keywords: | fibroblast growth factor 1 transcription factor RUNX2 Wnt10a protein ADAMTS protein ADAMTS2 protein, human DCN protein, human decorin FBN1 protein, human fibrillin 1 KERA protein, human LUM protein, human Transforming Growth Factor beta2 lumican proteoglycan TGFB2 protein, human transforming growth factor beta2 collagen complexity eye genetic analysis genome meta-analysis ADAMTS2 gene ADAMTS6 gene Article case control study central corneal thickness cohort analysis COL12A1 gene COL4A3 gene COL8A2 gene connective tissue controlled study cornea dystrophy Ehlers Danlos syndrome eye disease FAM46A gene FBN1 gene FNDC3B gene gene gene locus genome-wide association study human keratoconus Loeys Dietz syndrome LTBP1 gene major clinical study Marfan syndrome myopia NR3C2 gene open angle glaucoma RABGEF1 gene SAMD9 gene STAG1 gene TBL1XR1 gene TGFB2 gene THBS2 gene TIPARP gene abnormalities Asian continental ancestry group Caucasian congenital cornea dystrophy cornea cornea disease ethnology eye disease gene expression genetics human genome Mendelian randomization analysis meta analysis metabolism pathology quantitative trait quantitative trait locus single nucleotide polymorphism ADAMTS Proteins Asian Continental Ancestry Group Cornea Corneal Diseases Corneal Dystrophies, Hereditary Decorin Ehlers-Danlos Syndrome European Continental Ancestry Group Eye Diseases, Hereditary Fibrillin-1 Gene Expression Genome, Human Genome-Wide Association Study Glaucoma, Open-Angle Humans Keratoconus Loeys-Dietz Syndrome Lumican Marfan Syndrome Mendelian Randomization Analysis Myopia Polymorphism, Single Nucleotide Proteoglycans Quantitative Trait Loci Quantitative Trait, Heritable |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Citation: | Iglesias, A.I, Mishra, A, Vitart, V, etc. (2018). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nature Communications 9 (1) : 1864. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-03646-6 | Rights: | Attribution 4.0 International | Abstract: | Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation. © 2018 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/178412 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-018-03646-6 | Rights: | Attribution 4.0 International |
| Appears in Collections: | Staff Publications Elements |
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