Multi-omics Integration in AMD: the CFH Gene Case Study
DOI:
https://doi.org/10.61173/e328em58Keywords:
Age-related macular degeneration, CFH gene, multi-omics integration, GWAS, eQTL, colocalizationAbstract
Age-related macular degeneration (AMD) is a progressive retinal disease and a leading cause of irreversible blindness in older adults, imposing a substantial global health burden. Genome-wide association studies (GWAS) have identified over 50 loci associated with AMD, yet most lie in non-coding regions, obscuring the underlying molecular mechanisms. This paper highlights the application of multiomics integration—a framework that combines genetic associations with regulatory and functional outcomes across molecular layers—to elucidate the genetic risk of AMD, with a particular focus on the CFH gene, a central player in AMD pathogenesis. This study first summarizes key omics data types (genomics, transcriptomics, epigenomics) and core analytical tools, such as colocalization analysis and expression quantitative trait loci (eQTL) mapping. This then examines CFH-centered multi-omics findings, including evidence of shared causal variants between AMD GWAS and CFH eQTLs, and tissue-specific regulatory effects observed in the liver and retinal pigment epithelium. The discussion further extends to other AMD loci (e.g., ARMS2/HTRA1, C3) and outlines technical challenges such as data heterogeneity, tissue accessibility and translational potential. Overall, despite existing complexities, multi-omics integration provides an essential bridge between genetic associations and disease mechanisms, offering a roadmap for improved risk prediction and the development of mechanism-driven, biomarker-based therapeutics for AMD.
References
[1] Wong, W. L., et al. (2021). Global prevalence of age-related macular degeneration. The Lancet Global Health, 9(2), e106– e116.
[2] Ambati, J., & Fowler, B. J. (2012). Mechanisms of agerelated macular degeneration. Neuron, 75(1), 26–39.
[3] Fritsche, L. G., et al. (2016). A large meta-analysis of AMD identifies 52 genetic loci. Nature Genetics, 48(2), 134–143.
[4] Fritsche, L. G., et al. (2014). Complement factor H-related protein genes in AMD susceptibility. Human Molecular Genetics, 23(22), 5832–5843.
[5] Gamazon, E. R., & Stranger, B. E. (2015). The impact of human regulatory variation on complex traits. Science, 347(6226), 1518–1521.
[6] Li, X., et al. (2022). Multi-omics approaches for complex disease studies. Trends in Genetics, 38(6), 561–576.
[7] Zipfel, P. F., et al. (2020). Complement factor H and related proteins in AMD. Frontiers in Immunology, 11, 608.
[8] Edwards, A. O., et al. (2005). Complement factor H polymorphism and age-related macular degeneration. Science, 308(5720), 421–424.
[9] Haines, J. L., et al. (2005). Complement factor H variant increases the risk of age-related macular degeneration. Science, 308(5720), 419–421.
[10] Ratnapriya, R., et al. (2019). Retinal transcriptome and eQTL analyses identify genes associated with AMD. Nature Genetics, 51(4), 606–616.
[11] Chu, C., et al. (2021). Integrative analysis of genetic and transcriptomic data identifies causal genes for AMD. Nature Communications, 12, 7031.
[12] Deangelis, M. M., Silveira, A. C., Carr, E. A., & Kim, I. K. (2018). Genetics of age-related macular degeneration: current concepts, future directions. Seminars in Ophthalmology, 33(5), 705–712.
[13] Sun, B. B., et al. (2018). Genomic atlas of the human plasma proteome. Nature, 558(7708), 73–79.
[14] Khawaja, A. P., et al. (2020). Genetic risk prediction for age-related macular degeneration using functional genomic annotations. PLoS Genetics, 16(4), e1008955.
[15] Liao, D. S., et al. (2023). Complement inhibition in AMD: clinical development and prospects. Ophthalmology Retina, 7(3), 202–215.
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