A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration

Kawashima-Kumagai, Kyoko; Yamashiro, Kenji; Yoshikawa, Munemitsu; Miyake, Masahiro; Ming, Gemmy Cheung Chui; Fan, Qiao; Koh, Jia Yu; Saito, Masaaki; Sugahara-Kuroda, Masako; Oishi, Maho; Akagi-Kurashige, Yumiko; Nakata, Isao; Nakanishi, Hideo; Gotoh, Noriko; Oishi, Akio; Tamura, Hiroshi; Ooto, Sotaro; Tsujikawa, Akitaka; Kurimoto, Yasuo; Sekiryu, Tetsuju; Matsuda, Fumihiko; Khor, Chiea Chuen; Cheng, Ching‐Yu; Wong, Tien Yin; Yoshimura, Nagahisa

doi:10.1038/s41598-017-07526-9

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…The graph rendering clearly shows a fair number of reads aligning to these SNVs, forming a pileup that fails to appear in the reference graph. Moreover, this interval is within the third intron of STON1-GTF2A1L, a gene that appears in two GWAS studies linking it to neovascular age-related macular degeneration [24] and polycystic ovary syndrome [25]. Examples like this suggest that GPGs may improve our understanding of gene regulation in individual genomes.…”

Section: Further Characterizing the Altered Peaksmentioning

confidence: 98%

Personalized and graph genomes reveal missing signal in epigenomic data

Groza

Kwan

Soranzo

et al. 2018

Preprint

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Background: Epigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human genome, we hypothesized that using a generic reference could lead to incorrectly mapped reads and bias downstream results.Results: We show that accounting for genetic variation using a modified reference genome (MPG) or a denovo assembled genome (DPG) can alter histone H3K4me1 and H3K27ac ChIP-seq peak calls by either creating new personal peaks or by the loss of reference peaks. MPGs are found to alter approximately 1% of peak calls while DPGs alter up to 5% of peaks. We also show statistically significant differences in the amount of reads observed in regions associated with the new, altered and unchanged peaks. We report that short insertions and deletions (indels), followed by single nucleotide variants (SNVs), have the highest probability of modifying peak calls. A counter-balancing factor is peak width, with wider calls being less likely to be altered. Next, because high-quality DPGs remain hard to obtain, we show that using a graph personalized genome (GPG), represents a reasonable compromise between MPGs and DPGs and alters about 2.5% of peak calls. Finally, we demonstrate that altered peaks have a genomic distribution typical of other peaks. For instance, for H3K4me1, 518 personal-only peaks were replicated using at least two of three approaches, 394 of which were inside or within 10Kb of a gene.Conclusions: Analysing epigenomic datasets with personalized and graph genomes allows the recovery of new peaks enriched for indels and SNVs. These altered peaks are more likely to differ between individuals and, as such, could be relevant in the study of various human phenotypes.

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Section: Further Characterizing the Altered Peaksmentioning

confidence: 98%

Personalized and graph genomes reveal missing signal in epigenomic data

Groza

Kwan

Soranzo

et al. 2018

Preprint

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“…Genetic associations with clinical course and treatment outcome for AMD have been eagerly investigated, although prospective study has been performed rarely [ 186 ]. Many studies have suggested that ARMS2/HTRA1 polymorphisms can predict neovascular AMD bilaterality or fellow eye development [ 187 , 188 , 189 , 190 , 191 , 192 ], although this has not been fully confirmed [ 193 ]. In PCV, ARMS2/HTRA1 might be able to predict the occurrence of subretinal or vitreous hemorrhages [ 189 , 194 ].…”

Section: Personalized/precision Medicine For Cscmentioning

confidence: 99%

Characteristics of Pachychoroid Diseases and Age-Related Macular Degeneration: Multimodal Imaging and Genetic Backgrounds

Yamashiro

Hosoda

Miyake

et al. 2020

JCM

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The emergence of pachychoroid disease is changing the concept of age-related macular degeneration (AMD). The concept of pachychoroid diseases was developed through clinical observation of multimodal images of eyes with AMD and central serous chorioretinopathy; however, recent genetic studies have provided a proof of concept for pachychoroid spectrum disease, which should be differentiated from drusen-driven AMD. The genetic confirmation of pachychoroid concept further provides novel viewpoints to decode previously reported findings, which facilitates an understanding of the true nature of pachychoroid diseases and AMD. The purpose of this review was to elucidate the relationship between pachychoroid diseases and AMD by interpreting previous findings on pachychoroid diseases and AMD from the novel viewpoints of genetic associations. We confirmed that previous genetic studies supported the concept of pachychoroid diseases. From a genetic viewpoint, the presence of thick choroid and the presence of choroidal vascular hyperpermeability were important characteristics of pachychoroid spectrum diseases. Previous studies have also suggested the classification of polypoidal choroidal vasculopathy (PCV) into two subtypes, pachychoroid neovasculopathy and drusen-driven PCV. Genetic viewpoints will be beneficial to rearrange subtypes of drusen-driven AMD and pachychoroid spectrum diseases. Further genetic studies are needed to investigate pachyvessels, pachydrusen and the significance of polypoidal lesions in pachychoroid neovasculopathy and drusen-driven AMD/PCV.

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“…The graph rendering clearly shows a fair number of reads aligning to these SNVs, forming a pileup that fails to appear in the reference graph. Moreover, this interval is within the third intron of STON1-GTF2A1L, a gene that appears in two GWAS studies linking it to neovascular age-related macular degeneration [28] and polycystic ovary syndrome [29]. Such examples justify investigating whether GPGs could improve our understanding of gene regulation in individual genomes.…”

Section: Further Characterizing the Altered Peaksmentioning

confidence: 99%

Personalized and graph genomes reveal missing signal in epigenomic data

et al. 2020

View full text Add to dashboard Cite

Background: Epigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human genome, we hypothesize that using a generic reference could lead to incorrectly mapped reads and bias downstream results. Results: We show that accounting for genetic variation using a modified reference genome or a de novo assembled genome can alter histone H3K4me1 and H3K27ac ChIP-seq peak calls either by creating new personal peaks or by the loss of reference peaks. Using permissive cutoffs, modified reference genomes are found to alter approximately 1% of peak calls while de novo assembled genomes alter up to 5% of peaks. We also show statistically significant differences in the amount of reads observed in regions associated with the new, altered, and unchanged peaks. We report that short insertions and deletions (indels), followed by single nucleotide variants (SNVs), have the highest probability of modifying peak calls. We show that using a graph personalized genome represents a reasonable compromise between modified reference genomes and de novo assembled genomes. We demonstrate that altered peaks have a genomic distribution typical of other peaks. Conclusions: Analyzing epigenomic datasets with personalized and graph genomes allows the recovery of new peaks enriched for indels and SNVs. These altered peaks are more likely to differ between individuals and, as such, could be relevant in the study of various human phenotypes.

show abstract

A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration

Cited by 8 publications

References 37 publications

Personalized and graph genomes reveal missing signal in epigenomic data

Personalized and graph genomes reveal missing signal in epigenomic data

Characteristics of Pachychoroid Diseases and Age-Related Macular Degeneration: Multimodal Imaging and Genetic Backgrounds

Personalized and graph genomes reveal missing signal in epigenomic data

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