Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

Antisense oligonucleotides(ASOs) are a novel class of small molecule gene-targeted drugs that can bind with target mRNA. Through complementary base pairing with the target sequence, antisense oligonucleotides achieve targeted regulation of genes. With the continuous development of gene sequencing technology and molecular synthesis techniques, research and applications of ASOs in the musculoskeletal system have further advanced. This article reviews the mechanisms of ASOs in gene silencing and expression regulation, as well as their prospects in gene therapy. It also evaluates the research progress and applications of ASOs in musculoskeletal diseases and analyzes the urgent issues currently faced by this class of drugs. This comprehensive study aims to deepen our understanding of ASOs and provide valuable reference for their widespread application in biomedical research and clinical settings.

Congenital scoliosis (CS) is a congenital spinal deformity that originates from abnormal spinal development in embryo. Characterized by rapid progression, severe deformity, and many complications, CS brings heavy economic and mental burden to patients and their families. At present, there is no good treatment for the etiology of spinal deformity. Due to the lack of early prediction methods, patients are often not detected until the appearance of malformation, and the treatment is mainly passive, conservative or traumatic treatment with braces or surgery to control the progression of the disease. Therefore, the exploration of early diagnosis methods and effective etiological intervention targets for spinal deformity is currently an international research hotspot. The orthopaedic team of Peking Union Medical College Hospital, focusing on the molecular genetics research and clinical application of CS, has built the world leading genetic research system of skeletal deformity. Through a multi-center large-scale cohort study, the team has found and demonstrated that compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 led to CS. A set of genotype-phenotype integrated analysis method has been established, which successfully defined a new subtype of CS (TBX6-associated congenital scoliosis, TACS) and realized accurate clinical prediction of this unique subtype. With the establishment of the first genetics clinic of skeletal deformity in China, the clinical transformation of research results can thus be realized, providing a new paradigm for the etiology research and clinical application of skeletal deformity.