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Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration
Open accessAbstract
Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to age-related macular degeneration (AMD)1-3. We generated transcriptional profiles of postmortem retinas from 453 controls and cases at distinct stages of AMD and integrated retinal transcriptomes, covering 13,662 protein-coding and 1,462 noncoding genes, with genotypes at more than 9 million common SNPs for expression quantitative trait loci (eQTL) analysis of a tissue not included in Genotype-Tissue Expression (GTEx) and other large datasets 4,5. Cis-eQTL analysis identified 10,474 genes under genetic regulation, including 4,541 eQTLs detected only in the retina. Integrated analysis of AMD-GWAS with eQTLs ascertained likely target genes at six reported loci. Using transcriptome-wide association analysis (TWAS), we identified three additional genes, RLBP1, HIC1 and PARP12, after Bonferroni correction. Our studies expand the genetic landscape of AMD and establish the Eye Genotype Expression (EyeGEx) database as a resource for post-GWAS interpretation of multifactorial ocular traits.
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“In the retina, S2R is expressed in several cell types including the retinal pigment epithelium cells, photoreceptors, and retinal ganglion cells [70,71,72,73,74].”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [72]
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Cited by
Sorted by citations
Age-related macular degeneration
Fleckenstein, M., Keenan, T. D. L., Guymer, R. H., Chakravarthy, U., Schmitz-Valckenberg, S., Klaver, C. C. W., Wong, W. T., & Chew, E. Y. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00265-2 · Cited by 1,093
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Cao, C., Wang, J., Kwok, D., Cui, F., Zhang, Z., Da, Z., Li, M. J., & Zou, Q. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab957 · Cited by 365
“Biologists have used these emerging TWAS software packages to identify and interpret causal genes in multiple diseases and domains, such as calcific aortic valve stenosis (19), high-grade serous ovarian cancer (20), breast cancer (21), macular degeneration (22) and schizophrenia (23–26).”
MethodHysi, P. G., Choquet, H., Khawaja, A. P., Wojciechowski, R., Tedja, M. S., Yin, J., Simcoe, M. J., Patasova, K., Mahroo, O. A., Thai, K. K., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0599-0 · Cited by 334
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“multisubunit protein complex, has been linked with AMD risk [70].”
BackgroundRetinal organoids: a window into human retinal development
O’Hara-Wright, M., & Gonzalez-Cordero, A. (2020) · Development · doi:10.1242/dev.189746 · Cited by 169
Microglia versus Monocytes: Distinct Roles in Degenerative Diseases of the Retina
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Pluripotent stem cell-derived retinal organoids for disease modeling and development of therapies
Kruczek, K., & Swaroop, A. (2020) · Stem Cells · doi:10.1002/stem.3239 · Cited by 148
Self-citationWinkler, T. W., Grassmann, F., Brandl, C., Kiel, C., Günther, F., Strunz, T., Weidner, L., Zimmermann, M. E., Korb, C. A., Poplawski, A., et al. (2020) · BMC Medical Genomics · doi:10.1186/s12920-020-00760-7 · Cited by 138
“(29)) or in 44 other tissues (Genotype-Tissue Expression database, GTEx (30)).”
BackgroundMethodLarge-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci
Han, X., Gharahkhani, P., Hamel, A. R., Ong, J., Rentería, M. E., Mehta, P. A., Dong, X., Pasutto, F., Hammond, C. J., Young, T. L., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01428-5 · Cited by 158
Brooks, M. J., Chen, H. Y., Kelley, R. A., Mondal, A. K., Nagashima, K., de Val, N., Li, T., Chaitankar, V., & Swaroop, A. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.09.009 · Cited by 109
Self-citationGlutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration
Sreekumar, P. G., Ferrington, D. A., & Kannan, R. (2021) · Antioxidants · doi:10.3390/antiox10050661 · Cited by 107
“A recent study of the transcriptional profiles from 453 human donor retinas reported the expression of these two mitochondrial GSH carriers (SLC25A10 and SLC25A11), thereby corroborating the findings in murine retina [102].”
BackgroundSelf-citationHardcastle, A. J., Lišková, P., Bykhovskaya, Y., McComish, B. J., Davidson, A. E., Inglehearn, C. F., Li, X., Choquet, H., Habeeb, M., Lucas, S. E. M., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01784-0 · Cited by 100
Hamel, A. R., Yan, W., Rouhana, J. M., Monavarfeshani, A., Jiang, X., Mehta, P. A., Advani, J., Luo, Y., Liang, Q., Rajasundaram, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44380-y · Cited by 100
“…to POAG risk and IOP variation, we tested whether cis -eQTLs and cis -sQTLs (e/sQTLs) from 49 GTEx (v8) tissues 26 and peripheral retina cis -eQTLs 27 were enriched for POAG or IOP associations (GWAS P 0.05) using QTLEnrich 24,26 that adjusts for confounding factors and tissue sample size…”
BackgroundMethodInfluentialSelf-citationGenome-wide meta-analysis identifies novel loci associated with age-related macular degeneration
Han, X., Gharahkhani, P., Mitchell, P., Liew, G., Hewitt, A. W., & MacGregor, S. (2020) · Journal of Human Genetics · doi:10.1038/s10038-020-0750-x · Cited by 94
Relating enhancer genetic variation across mammals to complex phenotypes using machine learning
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Degtyareva, A. O., Antontseva, E. V., & Merkulova, T. I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126454 · Cited by 101
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“We also analyzed our list of SNPs using published human retina eQTL data from the Eye Genotype Expression (EyeGEx) database.(15) For more than 90% of SNPs in scATAC peaks, retina eQTL data were available (Figure 5B), enabling genes whose mRNA expression in the human retina changed with specific SNPs to be identified a…”
MethodBecker, K., Klein, H., Simon, E., Viollet, C., Haslinger, C., Leparc, G., Schultheis, C., Chong, V. N., Kuehn, M. H., Fernández-Albert, F., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-88698-3 · Cited by 87
Han, X., Steven, K., Qassim, A., Marshall, H. N., Bean, C., Tremeer, M., An, J., Siggs, O. M., Gharahkhani, P., Craig, J. E., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.05.005 · Cited by 79
“46,47 We also used the Eye-GEx database to perform a summary data-based Mendelian randomization (SMR) to investigate the association of gene expression levels (exposure) and phenotype (outcome).”
MethodMuSiC2: cell-type deconvolution for multi-condition bulk RNA-seq data
Fan, J., Lyu, Y., Zhang, Q., Wang, X., Li, M., & Xiao, R. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac430 · Cited by 74
Aging of the eye: Lessons from cataracts and age-related macular degeneration
Cvekl, A., & Vijg, J. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102407 · Cited by 77
“To find additional risk variants, RNA expression and eQTL-GWAS (Ratnapriya et al., 2019; Orozco et al., 2020), DNA methylation (Porter et al., 2019), chromatin accessibility (Wang et al.,”
BackgroundImplications of genetic variation in the complement system in age-related macular degeneration
de Jong, S., Gagliardi, G., Garanto, A., de Breuk, A., Lechanteur, Y. T. E., Katti, S., van den Heuvel, L. P., Volokhina, E. B., & den Hollander, A. I. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100952 · Cited by 71
“Two recent studies have explored the effect of AMD-associated genetic variants on gene expression levels in the retina and RPE (Orozco et al., 2020; Ratnapriya et al., 2019).”
BackgroundSenabouth, A., Daniszewski, M., Lidgerwood, G. E., Liang, H. H., Hernández, D., Mirzaei, M., Keenan, S. N., Zhang, R., Han, X., Neavin, D. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31707-4 · Cited by 75
Power analysis of transcriptome-wide association study: Implications for practical protocol choice
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Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions
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Self-citationStrunz, T., Lauwen, S., Kiel, C., International AMD Genomics Consortium (IAMDGC), Fritsche, L. G., Igl, W., Bailey, J. N. C., Grassmann, F., Sengupta, S., Bragg-Gresham, J. L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-58510-9 · Cited by 60
Self-citationProline metabolism and transport in retinal health and disease
Du, J., Zhu, S., Lim, R. R., & Chao, J. R. (2021) · Amino Acids · doi:10.1007/s00726-021-02981-1 · Cited by 66
A mega-analysis of expression quantitative trait loci in retinal tissue
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“Genotypes of the Bethesda dataset were processed as described earlier [7].”
BackgroundMethodInfluentialSelf-citationMulti-omics study for interpretation of genome-wide association study
Akiyama, M. (2020) · Journal of Human Genetics · doi:10.1038/s10038-020-00842-5 · Cited by 63
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“A comparison with previous TWAS studies 51,56 is summarized in Supplementary Table 28.”
Self-citationMarchal, C., Singh, N., Batz, Z. A., Advani, J., Jaeger, C., Corso‐Díaz, X., & Swaroop, A. (2022) · Nature Communications · doi:10.1038/s41467-022-33427-1 · Cited by 54
Self-citationHe, W., Han, X., Ong, J., Wu, Y., Hewitt, A. W., Mackey, D. A., Gharahkhani, P., & MacGregor, S. (2023) · Ophthalmology · doi:10.1016/j.ophtha.2023.08.023 · Cited by 61
Advani, J., Mehta, P. A., Hamel, A. R., Mehrotra, S., Kiel, C., Strunz, T., Corso‐Díaz, X., Kwicklis, M., van Asten, F., Ratnapriya, R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46063-8 · Cited by 58
“We also performed concurrent cis -eQTL analysis from 403 retinas with genotype and RNA-seq data from the same study 32 correcting for covariates (see Methods).”
InfluentialSelf-citationCao, C., Kwok, D., Edie, S., Li, Q., Ding, B., Kossinna, P., Campbell, S., Wu, J., Greenberg, M., & Long, Q. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa270 · Cited by 56
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A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration
Orozco, L. D., Owen, L. A., Hofmann, J. W., Stockwell, A., Tao, J., Haller, S., Mukundan, V. T., Clarke, C., Lund, J. M., Sridhar, A., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100302 · Cited by 51
“Our results indicate that M€ uller gliosis is not a general feature of AMD, consistent with studies of bulk RNA-seq in AMD retina.(10,30) This observation highlights the molecular discrepancy between retinal injury models often used in AMD translational research and the actual human disease state,(54) which may bemisl…”
ResultMTOR‐initiated metabolic switch and degeneration in the retinal pigment epithelium
Go, Y., Zhang, J., Fernandes, J., Litwin, C., Chen, R., Wensel, T. G., Jones, D. P., Cai, J., & Chen, Y. (2020) · The FASEB Journal · doi:10.1096/fj.202000612r · Cited by 52
Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes
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“Notably, like other complex disease traits including age-related macular degeneration (Fritsche et al., 2014; Fritsche et al., 2016), a majority of genetic variants nominally associated with diabetic retinopathy are located in intronic or inter-genic regions (Risch and Merikangas, 1996).”
BackgroundSelf-citationLyu, Y., Zauhar, R. J., Dana, N., Strang, C. E., Hu, J., Wang, K., Liu, S., Pan, N., Gamlin, P. D., Kimble, J. A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-95122-3 · Cited by 47
Splicing mutations in inherited retinal diseases
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“Expression quantitative trait (eQTL) analysis To uncover the molecular mechanisms of DR susceptibility, we examined the association of the lead SNPs and gene expression in various tissues by searching publicly available eQTL database, GTEx (20), and Eye Genotype Expression database, EyeGEx (21) (Supplementary Material…”
MethodInfluentialMulti-omic spatial effects on high-resolution AI-derived retinal thickness
Jackson, V. E., Wu, Y., Bonelli, R., Owen, J. P., Scott, L. W., Farashi, S., Kihara, Y., Gantner, M. L., Egan, C. A., Williams, K. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55635-7 · Cited by 35
“The FPC-based RT association analyses identi fi ed 127 independently associated SNPs at 120 loci (Sup-plementaryData2),with4,11,36,45,42,23locimeeting p 8.33e-9for FPCs 1 to 6, respectively (Fig.”
InfluentialCavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca2+ channel function
Erdogmus, S., Concepcion, A. R., Yamashita, M., Sidhu, I., Tao, A. Y., Li, W., Rocha, P. P., Huang, B., Garippa, R. J., Lee, B. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29725-3 · Cited by 41
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Family-based exome sequencing identifies rare coding variants in age-related macular degeneration
Ratnapriya, R., Acar, İ. E., Geerlings, M. J., Branham, K. E. H., Kwong, A. M., Saksens, N. T. M., Pauper, M., Corominas, J., Kwicklis, M., Zipprer, D., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa057 · Cited by 37
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“The Ame riya et al.(20) A total of 453 samples that passed quality control were considered first.”
BackgroundSystems genomics in age-related macular degeneration
den Hollander, A. I., Mullins, R. F., Orozco, L. D., Voigt, A. P., Chen, H.-H., Strunz, T., Graßmann, F., Haines, J. L., Kuiper, J. J. W., Tumminia, S. J., et al. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2022.109248 · Cited by 38
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Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma
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“The bulk retinal transcriptome data were described previously.(78) Of the three genes with available bulk TWAS results, only KANSL1-AS1 was significant after Bonferroni correction (Pbulk TWAS = 5.”
BackgroundDisentangling genetic feature selection and aggregation in transcriptome-wide association studies
Cao, C., Kossinna, P., Kwok, D., Li, Q., He, J., Su, L., Guo, X., Zhang, Q., & Long, Q. (2021) · Genetics · doi:10.1093/genetics/iyab216 · Cited by 35
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“To evaluate the impact of SVs on retina-speci fi c transcripts, we utilized RNA-seq data from 120 normal retinal samples 33 , which were part of GTEx external datasets.”
Sex-stratified genome-wide association meta-analysis of major depressive disorder
Thomas, J. T., Thorp, J. G., Huider, F., Grimes, P. Z., Wang, R., Youssef, P., Coleman, J. R. I., Byrne, E. M., Adams, M. J., van Loo, H. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63236-1 · Cited by 36
Single-cell atlas of the transcriptome and chromatin accessibility in the human retina
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“The variant was predicted to strengthen HSF1 binding, potentially enhancing CLIC5 expression in MG, consistent with the variant’s effect direction in the eQTL analysis 64 (slope = 0.6, P = 7.2 × 10 −18 ).”
InfluentialFaro, V. L., Bhattacharya, A., Zhou, W., Zhou, D., Wang, Y., Läll, K., Kanai, M., Lopera-Maya, E. A., Straub, P., Pawar, P. P., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101430 · Cited by 37
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“We looked up the lead DD genome-wide significant SNPs in retina from the Eye Genotype Expression (EyeGEx) database to identify eQTL (32).”
BackgroundJanecke, A., Liu, X., Adam, R., Punuru, S., Viestenz, A., Strauß, V., Laass, M. W., Sánchez, E., Adachi, R., Schatz, M. P., et al. (2021) · Human Genetics · doi:10.1007/s00439-021-02284-1 · Cited by 32
Eye in a Disk: eyeIntegration Human Pan-Eye and Body Transcriptome Database Version 1.0
Swamy, V. S., & McGaughey, D. M. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.19-27106 · Cited by 31
The role of microRNAs in glaucoma
Greene, K. M., Stamer, W. D., & Liu, Y. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108909 · Cited by 30
Subhi, Y., Nielsen, M. K., Molbech, C. R., Liisborg, C., Søndergaard, H. B., Sellebjerg, F. T., & Sørensen, T. L. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0160-0 · Cited by 30
García-Cruz, C., Aragón, J., Lourdel, S., Annan, A., Roger, J. E., Montáñez, C., & Vaillend, C. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac236 · Cited by 30
“For analysis of expression in human whole retina, we used a published transcriptomic database ((67); GEO accession # GSE115828).”
MethodMarkitantova, Y. V., & Simirskii, V. N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310776 · Cited by 30
“A recent study of the RPE transcriptome in the macula and periphery of the retina, obtained using microarray technology, revealed differential expression of extracellular matrix (ECM) protein genes in MBs, which reflects the functional state of this structure [33].”
BackgroundLiu, B., Calton, M. A., Abell, N. S., Benchorin, G., Gloudemans, M. J., Chen, M., Hu, J. G., Li, X., Balliu, B., Bok, D., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0430-6 · Cited by 30
sn-spMF: matrix factorization informs tissue-specific genetic regulation of gene expression
He, Y. M., Chhetri, S. B., Arvanitis, M., Srinivasan, K., Aguet, F., Ardlie, K., Barbeira, A., Bonazzola, R., Im, H. K., Brown, C. D., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02129-6 · Cited by 28
Self-citationBronstein, R., Capowski, E. E., Mehrotra, S., Jansen, A. D., Navarro-Gomez, D., Maher, M., Place, E., Sangermano, R., Bujakowska, K. M., Gamm, D. M., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa016 · Cited by 27
Homeostatic maintenance and age-related functional decline in the Drosophila ear
Keder, A., Tardieu, C. H., Malong, L., Filia, A., Kashkenbayeva, A., Newton, F. G., Georgiades, M., Gale, J. E., Lovett, M., Jarman, A. P., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-64498-z · Cited by 24
Burns, A. C., Phillips, A. J. K., Rutter, M. K., Saxena, R., Cain, S. W., & Lane, J. M. (2022) · SLEEP · doi:10.1093/sleep/zsac287 · Cited by 27
Su, J., Yuan, J., Xu, L., Xing, S., Sun, M., Yao, Y., Ma, Y., Chen, F., Jiang, L., Li, K., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112510 · Cited by 25
Ascari, G., Rendtorff, N. D., Bruyne, M. D., Zaeytijd, J. D., Lint, M. V., Bauwens, M., Heetvelde, M. V., Arno, G., Jacob, J. A., Creytens, D., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.664317 · Cited by 25
Learning from Fifteen Years of Genome-Wide Association Studies in Age-Related Macular Degeneration
Strunz, T., Kiel, C., Sauerbeck, B. L., & Weber, B. H. F. (2020) · Cells · doi:10.3390/cells9102267 · Cited by 24
“Second, a mega-analysis of eQTL in 311 retinal tissues, which also included the healthy donor samples of Ratnapriya et al. (2019) [32].”
BackgroundMethodInfluentialMullin, N. K., Voigt, A. P., Boese, E. A., Liu, X., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2023) · American Journal Of Pathology · doi:10.1016/j.ajpath.2023.01.012 · Cited by 24
RNA sequencing analysis of the human retina and associated ocular tissues
Schumacker, S. T., Coppage, K. R., & Enke, R. A. (2020) · Scientific Data · doi:10.1038/s41597-020-0541-4 · Cited by 23
Antontseva, E. V., Degtyareva, A. O., Korbolina, E. E., Damarov, I. S., & Merkulova, T. I. (2023) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-23-77 · Cited by 28
“At present, quantitative expression trait loci analysis is mainly utilized to identify groups of genes participating in trait formation (Hormozdiari et al., 2016; Morrow et al., 2018; Gamazon et al., 2019; Ratnapriya et al., 2019; Jaffe et al., 2020).”
MethodWang, J., Cheng, X., Liang, Q., Owen, L. A., Lu, J., Zheng, Y., Wang, M., Chen, S., DeAngelis, M. M., Li, Y., et al. (2023) · Genome biology · doi:10.1186/s13059-023-03111-8 · Cited by 21
“Then we extracted the GWAS variants and retinal bulk eQTL variants [85] of the genes in the region and performed colocalization using the “coloc” R package (v5.”
MethodMechanisms and Advances of Epigenetic Regulation in Cardiovascular Disease
Wang, X., Teng, X., Luo, C., & Kong, L. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2906205 · Cited by 23
“Genome-wide association studies (GWAS) conducted in Europe and the United States have reported associations between more than 10 gene loci and blood pressure, but there are still many more genetic variants to discover [132].”
Epigenome–metabolism nexus in the retina: implications for aging and disease
Mondal, A. K., Gaur, M., Advani, J., & Swaroop, A. (2024) · Trends in Genetics · doi:10.1016/j.tig.2024.04.012 · Cited by 20
Self-citationBiphasic expression of thyroid hormone receptor TRβ1 in mammalian retina and anterior ocular tissues
Ng, L., Liu, H., Liu, Y., & Forrest, D. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1174600 · Cited by 21
Geographic atrophy: pathophysiology and current therapeutic strategies
Rajanala, K., Dotiwala, F., & Upadhyay, A. K. (2023) · Frontiers in Ophthalmology · doi:10.3389/fopht.2023.1327883 · Cited by 21
“…PILRB/PILRA (paired immunoglobin like type 2 receptor beta/ alpha), B3GLCT (beta 3-glucosyltransferase), BLOC1S1 (biogenesis of lysosome related organelles complex 1 subunit 1), TMEM199 (transmembrane protein 199), and TSPAN10 (tetraspanin 10) as additional putative causal genes for AMD (114, 115).”
BackgroundCopy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations
Besedina, E. G., & Supek, F. (2024) · Nature Communications · doi:10.1038/s41467-024-50552-1 · Cited by 21
Smith, A. J., Advani, J., Brock, D. C., Nellissery, J. K., Gumerson, J., Dong, L., Aravind, L., Kennedy, B. N., & Swaroop, A. (2022) · BMC Biology · doi:10.1186/s12915-022-01267-6 · Cited by 21
“The other datasets analyzed during the current study were from the Genotype-Tissue Expression Project, dbGaP Study Accession: phs000424.v7.p2 [16, 70] and NCBI GEO accession GSE115828 [17, 71].”
BackgroundMethodInfluentialSelf-citationIncreased serum proteins in non-exudative AMD retinas
Schultz, H., Song, Y., Baumann, B. H., Kapphahn, R. J., Montezuma, S. R., Ferrington, D. A., & Dunaief, J. L. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.05.026 · Cited by 20
“However, this is unlikely to account for our results, as a database of AMD transcriptomics from peripheral NSR (Brooks et al., 2019; Ratnapriya et al., 2019) and macula (Kwicklis, M, and Swaroop, A, unpublished) showed no difference in albumin mRNA levels in the NSR of intermediate AMD (MGS3) eyes as compared to age-m…”
ResultSelf-citationDíaz‐Torres, S., He, W., Yu, R., Han, X., Hamel, A. R., Young, T. L., Lotery, A. J., Jorgenson, E., Choquet, H., Hauser, M. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54301-2 · Cited by 19
“…randomization (SMR) (Zhu et al. 42 ), v 1.3.1, to identify putative causal associations between gene expression and NTG based on eQTL data from peripheral blood of 2765 individuals from the Consortium for the Architecture of Gene Expression (CAGE) 43 and retinal eQTL data from 453 individuals 44 .”
InfluentialCo-Expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19
Yuan, J., Fan, D., Xue, Z., Qu, J., & Su, J. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.12.13 · Cited by 19
Retinal Transcriptome and Cellular Landscape in Relation to the Progression of Diabetic Retinopathy
Wang, J.-H., Wong, R. C. B., & Liu, G. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.9.26 · Cited by 19
Variability in Gene Expression is Associated with Incomplete Penetrance in Inherited Eye Disorders
Green, D. J., Sallah, S. R., Ellingford, J. M., Lovell, S. C., & Sergouniotis, P. I. (2020) · Genes · doi:10.3390/genes11020179 · Cited by 19
de Bruijn, S. E., Fadaie, Z., Cremers, F. P. M., Kremer, H., & Roosing, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062943 · Cited by 20
“, SHIELD [123], gEAR [124], EyeGEx [125]) and explore associated protein interaction networks (e.”
BackgroundTMEM97 ablation aggravates oxidant-induced retinal degeneration
Shen, H., Li, J., Heisler-Taylor, T., Makin, R., Yang, H., Mavlyutov, T. A., Gelfand, B., Cebulla, C. M., & Guo, L.-W. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110078 · Cited by 19
“Without follow-up functional studies available, it is unclear whether the TMEM97 variant could truly impact retinal degeneration, and it remains an interesting question whether the TMEM97 SNP (rs11080055) [5] could have a similar functional impact in the RPE as the TMEM97 KO observed here.”
BackgroundResultZampaglione, E., Maher, M., Place, E., Wagner, N. E., DiTroia, S. P., Chao, K. R., England, E. M., Broad, C. M. G., Catomeris, A. J., Nassiri, S., et al. (2021) · Genetics in Medicine · doi:10.1016/j.gim.2021.09.015 · Cited by 18
D’haene, E., López-Soriano, V., Martínez‐García, P. M., Kalayanamontri, S., Rey, A. D., Sousa‐Ortega, A., Naranjo, S., de Sompele, S. V., Vantomme, L., Mahieu, Q., et al. (2024) · Genome biology · doi:10.1186/s13059-024-03250-6 · Cited by 13
“This was in line with expectations, as the cell types found within the RPE/ choroid are also present in epithelial, connective, and vascular tissues throughout the human body, while the retinal tissue from the EyeGEx database primarily contains neural retina [30].”
BackgroundMethodResultInfluentialJiang, H., Limsuwannarot, S. P., Kulhanek, K. R., Pal, A., Labiad, O., Rysavy, L. W., Wong, A., Su, L., Cavender, S. M., Soro, J., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.10.024 · Cited by 18
Jones, A. V., MacGregor, S., Han, X., Francis, J. N., Harris, C. L., Kavanagh, D., Lotery, A. J., & Waheed, N. K. (2022) · Ophthalmology Science · doi:10.1016/j.xops.2022.100146 · Cited by 16
Akiyama, M., Miyake, M., Momozawa, Y., Arakawa, S., Maruyama-Inoue, M., Endo, M., Iwasaki, Y., Ishigaki, K., Matoba, N., Okada, Y., et al. (2022) · Ophthalmology · doi:10.1016/j.ophtha.2022.10.034 · Cited by 17
Green, D. J., Lenassi, E., Manning, C. S., McGaughey, D. M., Sharma, V., Black, G. C. M., Ellingford, J. M., & Sergouniotis, P. I. (2021) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.62.7.16 · Cited by 18
“34,35 We then queried the DESCARTES chromatin accessibility database for the location of NCMD-associated variants across all available tissues.”
Method
Metadata
- Authors
- Ratnapriya, R., Sosina, O. A., Starostik, M. R., Kwicklis, M., Kapphahn, R. J., Fritsche, L. G., Walton, A., Arvanitis, M., Gieser, L., Pietraszkiewicz, A., Montezuma, S. R., Chew, E. Y., Battle, A., Abecasis, G. R., Ferrington, D. A., Chatterjee, N., & Swaroop, A.
- Affiliations
- National Institutes of Health (US)
- University of Minnesota (US)
- University of Michigan (US)
- Johns Hopkins University (US)
- Corresponding author
- Ferrington, Deborah A.
- Chatterjee, Nilanjan
- Swaroop, Anand
- ORCID
- Venue
- Nature Genetics
- Published
- 2019-02-11
- Volume
- 51
- Issue
- 4
- Pages
- 606-610
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC6441365
- OpenAlex
- W2914762802
- Cited by
- 312
- References
- 56
- Citations by year
- 2026: 47 · 2025: 49 · 2024: 46 · 2023: 40 · 2022: 35 · 2021: 36 · 2020: 46 · 2019: 13
- FWCI
- 31.89
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-05-08)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Minnesota Lions Eye Bank
- University of Minnesota
- National Institutes of Health
- National Human Genome Research Institute (T32HG000040)
- National Eye Institute (ZIAEY000475, Z01EY000450, R01EY026012, ZIAEY000474, ZIAEY000450, R01EY028554)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, retinal transcriptome, expression quantitative trait loci, transcriptome-wide association study, cis-eQTL, RLBP1, HIC1, PARP12, non-coding RNA, ocular genetics
- MeSH terms
- Gene Expression Regulation, Genotype, Humans, Macular Degeneration, Phenotype, Retina, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Expression Profiling, Quantitative Trait Loci, Genome-Wide Association Study, Transcriptome
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