A genome-wide scan of non-coding RNAs and enhancers for refractive error and myopia DOI Creative Commons
Milly S. Tedja, Joanna Swierkowska, Clair A. Enthoven

et al.

Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Refractive error (RE) and myopia are complex polygenic conditions with the majority of genome-wide associated genetic variants in non-exonic regions. Given this, onset during childhood, gene-regulation is expected to play an important role its pathogenesis. This prompted us explore beyond traditional gene finding approaches. We performed a association study between non-coding RNAs enhancers, RE myopia. obtained single-nucleotide polymorphisms (SNPs) microRNA (miRNA) genes, miRNA-binding sites, long genes (lncRNAs) enhancers from publicly available databases: miRNASNPv2, PolymiRTS, VISTA Enhancer Browser, FANTOM5 lncRNASNP2. investigated whether SNPs overlapping these elements were leveraged large GWAS meta-analysis (N = 160,420). With risk scores (GRSs) per element, we joint effect on RE, axial length (AL)/corneal radius (CR), AL progression independent child cohort, Generation R Study 3638 children). constructed score for biological plausibility SNP highly confident sites chromatin accessible found that two miRNA 14 81 lncRNA regions 54 myopia-associated loci. GRSs significantly AL/CR progression. lncRNAs all miRNAs not any ocular biometric measurement. showed suggestive but inconsistent significance. prioritized candidate binding future functional validation. Pathways target host ranked included eye development (BMP4, MPPED2), neurogenesis (DDIT4, NTM), extracellular matrix (ANTXR2, BMP3), photoreceptor metabolism (DNAJB12), morphogenesis (CHDR1), neural signaling (VIPR2) TGF-beta (ANAPC16). first large-scale Enhancers could be importance as they childhood provide blueprint validation by prioritizing enhancers.

Language: Английский

A genome-wide scan of non-coding RNAs and enhancers for refractive error and myopia DOI Creative Commons
Milly S. Tedja, Joanna Swierkowska, Clair A. Enthoven

et al.

Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Refractive error (RE) and myopia are complex polygenic conditions with the majority of genome-wide associated genetic variants in non-exonic regions. Given this, onset during childhood, gene-regulation is expected to play an important role its pathogenesis. This prompted us explore beyond traditional gene finding approaches. We performed a association study between non-coding RNAs enhancers, RE myopia. obtained single-nucleotide polymorphisms (SNPs) microRNA (miRNA) genes, miRNA-binding sites, long genes (lncRNAs) enhancers from publicly available databases: miRNASNPv2, PolymiRTS, VISTA Enhancer Browser, FANTOM5 lncRNASNP2. investigated whether SNPs overlapping these elements were leveraged large GWAS meta-analysis (N = 160,420). With risk scores (GRSs) per element, we joint effect on RE, axial length (AL)/corneal radius (CR), AL progression independent child cohort, Generation R Study 3638 children). constructed score for biological plausibility SNP highly confident sites chromatin accessible found that two miRNA 14 81 lncRNA regions 54 myopia-associated loci. GRSs significantly AL/CR progression. lncRNAs all miRNAs not any ocular biometric measurement. showed suggestive but inconsistent significance. prioritized candidate binding future functional validation. Pathways target host ranked included eye development (BMP4, MPPED2), neurogenesis (DDIT4, NTM), extracellular matrix (ANTXR2, BMP3), photoreceptor metabolism (DNAJB12), morphogenesis (CHDR1), neural signaling (VIPR2) TGF-beta (ANAPC16). first large-scale Enhancers could be importance as they childhood provide blueprint validation by prioritizing enhancers.

Language: Английский

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