Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases

Liu, Kangcheng; Fan, Huimin; Hu, Hanying; Cheng, Yanhua; Liu, Jingying; You, Zhipeng

doi:10.3389/fendo.2022.1088557

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…Furthermore, POAG (3,412 cases and 210,201 controls) and PACG (588 cases and 210,201 controls) were included as histological subgroups for further comprehension of the causality between genetically predisposed AS and glaucoma subtypes. This study defines glaucoma by H40-H42 of the International Classification of Disease-10, and other studies have supported the use and accuracy of the International Classification of Disease coding for this diagnosis ( 28 , 29 ) ( Figure 1 ).…”

Section: Methodssupporting

confidence: 55%

Ankylosing spondylitis and glaucoma in European population: A Mendelian randomization study

Chen

Zhang

et al. 2023

Front. Immunol.

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BackgroundThe relationship between ankylosing spondylitis (AS) and glaucoma in the European population remains unclear. In the present study, we applied a two-sample Mendelian randomization (MR) method to investigate their causal relationship.MethodsMR analysis was conducted to validate the causal associations between AS with glaucoma using summary statistics from the genome-wide association studies of AS (9,069 cases and 13,578 control subjects) and glaucoma (8,591 cases and 210,201 control subjects). The inverse variance weighting method was performed to evaluate the causal relationship. The MR–Egger regression approach was applied to assess pleiotropy, while Cochran’s Q test was used to analyze heterogeneity. Subgroup analysis was performed according to primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).ResultsThe results of the MR study reveal a risk-increasing causal relationship between AS and glaucoma among European populations (OR = 1.35, 95%CI = 1.16–1.57, P = 8.81 × 10-5). Pleiotropy and heterogeneity were not found in our study. In the subgroup analysis, AS was also causal with POAG (OR = 1.48, 95%CI = 1.17–1.86, P = 8.80 × 10-4) and PACG (OR = 1.91, 95%CI = 1.03–3.51, P = 3.88 × 10-2).ConclusionThe results of the MR analysis suggested a causal relationship between AS and glaucoma in the European population. Further studies are needed to identify the specific mechanism between these two diseases.

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Section: Methodssupporting

confidence: 55%

Ankylosing spondylitis and glaucoma in European population: A Mendelian randomization study

Chen

Zhang

et al. 2023

Front. Immunol.

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“…A p -value <5×10 −8 was selected as the threshold for IVs for 25(OH)D, TT, and E2. On the other hand, p <1×10 −5 was selected as the threshold for IVs for A4 and T/E2 due to the relatively few IVs ( 21 ). Linkage disequilibrium was set to R 2 < 0.001 ( 22 ), and palindrome SNPs were deleted.…”

Section: Methodsmentioning

confidence: 99%

Roles of sex hormones in mediating the causal effect of vitamin D on osteoporosis: A two-step Mendelian randomization study

Xie²,

Wang

et al. 2023

Front. Endocrinol.

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BackgroundAlthough 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis, it is not clear whether sex hormones mediate this casual association. We aimed to explore how sex hormones affect the association between 25(OH)D and osteoporosis to provide meaningful insights on the underlying mechanisms from a genetic perspective.MethodsGenetic variations in 25(OH)D, total testosterone (TT), androstenedione (A4), estradiol (E2), and testosterone/17β-estradiol (T/E2) were determined through summary statistics. Taking osteoporosis as the outcome (FinnGen biobank, 332,020 samples), we conducted a Mendelian randomization (MR) analysis to establish the association between 25(OH)D and these sex hormones. The two-step MR analysis quantified the mediatory effects of sex hormones on osteoporosis. The results were further verified by pleiotropy and heterogeneity analyses.ResultsMR results showed that 25(OH)D (OR= 1.27, p = 0.04) and TT (OR= 1.25, p = 0.04) had a causal effect on osteoporosis. No significant associations were observed between the other sex hormones (A4, E2, and T/E2) and osteoporosis (p>0.05). Sensitivity analysis (p>0.05) confirmed the robustness of the MR results. The two-step MR analysis provided evidence that the mediatory effect of TT was 0.014 (the percentage of TT mediation was 5.91%). Moreover, the direct effect of 25(OH)D on osteoporosis was 0.221. A4, E2, and T/E2 were not considered as potential mediators of the role of 25(OH)D as a risk factor for OP.ConclusionThis study, through MR analysis, showed that TT mediates the causal effect of 25(OH)D on osteoporosis. Interventions targeting TT, therefore, have the potential to substantially reduce the burden of osteoporosis attributable to high 25(OH)D.

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“…6D-E, Supplementary Table 17). Complement pathways have been shown to play important roles in the pathogenesis of age-related macular degeneration (AMD) [42][43][44][45][46][47] , and alterations in steroid hormone homeostasis have been linked to glaucoma 48, 49 . In contrast, the common suppressed pathways included ribosome, cytoplasmic translation, mitochondrial gene expression, and ribonucleoprotein complex assembly, aligning with findings in a fly aging study 50 (Fig.…”

Section: Differential Gene Expression Associated With Age and Sexmentioning

confidence: 99%

Integrated multi-omics single cell atlas of the human retina

Chen,

Li,

Wang

et al. 2023

Preprint

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Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology.

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Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases

Cited by 6 publications

References 48 publications

Ankylosing spondylitis and glaucoma in European population: A Mendelian randomization study

Ankylosing spondylitis and glaucoma in European population: A Mendelian randomization study

Roles of sex hormones in mediating the causal effect of vitamin D on osteoporosis: A two-step Mendelian randomization study

Integrated multi-omics single cell atlas of the human retina

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