Publications by authors named "Nai-Ning Wang"

GWASs have identified many loci associated with osteoporosis, but the underlying genetic regulatory mechanisms and the potential drug target need to be explored. Here, a new regulatory mechanism is found that a GWAS intergenic SNP (rs4683184) functions as an enhancer to influence the binding affinity of transcription factor RUNX2, whose phase separation can mediate the long-range chromatin interaction between enhancer and target gene XCR1 (a member of the GPCR family), leading to changes of XCR1 expression and osteoblast differentiation. Bone-targeting AAV of Xcr1 can improve bone formation in osteoporosis mice, suggesting that XCR1 can be a new susceptibility gene for osteoporosis.

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The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition.

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Article Synopsis
  • Genome-wide association studies have linked certain non-coding SNPs at 2p14 to rheumatoid arthritis, but their functional roles weren't fully understood until now.
  • This study identified three specific intronic SNPs that regulate the expression of the gene SPRED2, which plays a crucial role in controlling the harmful behavior of cells involved in RA.
  • The interactions between SPRED2 and another protein, ACTR2, create a feedback loop that enhances protection against RA, suggesting SPRED2 as a potential target for more precise RA treatments.
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Background: Accumulative evidences have shown that dysregulation of biological pathways contributed to the initiation and progression of malignant tumours. Several methods for pathway activity measurement have been proposed, but they are restricted to making comparisons between groups or sensitive to experimental batch effects.

Methods: We introduced a novel method for individualized pathway activity measurement (IPAM) that is based on the ranking of gene expression levels in individual sample.

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Thyroid dysfunction is a common endocrine disease measured by thyroid-stimulating hormone (TSH) level. Although >70 genetic loci associated with TSH have been reported through genome-wide association studies (GWASs), the variants can only explain a small fraction of the thyroid function heritability. To identify novel candidate genes for thyroid function, we conducted the first large-scale transcriptome-wide association study (TWAS) for thyroid function using GWAS-summary data for TSH levels in up to 119 715 individuals combined with precomputed gene expression weights of six panels from four tissue types.

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Motivation: CircRNAs are an abundant class of non-coding RNAs with widespread, cell-/tissue-specific patterns. Previous work suggested that epigenetic features might be related to circRNA expression. However, the contribution of epigenetic changes to circRNA expression has not been investigated systematically.

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Both systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are autoimmune diseases sharing similar genetic backgrounds. Genome-wide association studies have constantly disclosed numerous genetic variants conferring to both disease risks at 7q32.1, but the functional mechanisms underlying them are still largely unknown.

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RANKL is a key regulator involved in bone metabolism, and a drug target for osteoporosis. The clinical diagnosis and assessment of osteoporosis are mainly based on bone mineral density (BMD). Previous powerful genomewide association studies (GWASs) have identified multiple intergenic single-nucleotide polymorphisms (SNPs) located over 100 kb upstream of RANKL and 65 kb downstream of AKAP11 at 13q14.

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