青少年特发性脊柱侧凸队列的全基因组测序揭示了多种生物学途径。

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2025-10-10 DOI:10.1038/s41525-025-00520-5

Islam Oguz Tuncay, Eun Kyoung Lee, Anxhela Gustafson, Yoonsuh Lee, Dawoon Jung, June-Young Koh, Wonchul Lee, Sangmoon Lee, Kamran Shazand

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引用次数: 0

摘要

青少年特发性脊柱侧凸（AIS）是一种复杂的遗传疾病。本研究采用全基因组测序（WGS）对103个家庭的119例AIS患者的遗传基础进行了研究。我们的WGS分析在15个先证中发现了已知的致病性或蛋白质截断变异，在另外69个患者中发现了其他强或中等候选变异。我们发现了编码和非编码突变，包括结构变异。候选基因包括已知的AIS基因（如COL11A2、FBN1）和与脊柱侧凸相关的其他肌肉骨骼疾病相关的基因（如RYR1）。关联分析在我们的队列中证实了4个已知的AIS单核苷酸多态性。基因集富集分析揭示了骨骼肌收缩、细胞外基质和基因表达调控相关的四个基因簇。这种基于wgs的方法确定了AIS患者的临床相关遗传变异和生物学途径，为其复杂的发展提供了有价值的见解。

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Whole genome sequencing in adolescent idiopathic scoliosis cohort implicates multiple biological pathways.

Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder. This study used whole-genome sequencing (WGS) to investigate the genetic basis of AIS in 119 patients from 103 families. Our WGS analysis identified known pathogenic or protein-truncating variants in 15 probands, and other strong or moderate candidate variants in 69 additional patients. We found both coding and non-coding mutations, including structural variants. Candidate genes included known AIS genes (e.g., COL11A2, FBN1) and genes linked to other musculoskeletal disorders with scoliosis (e.g., RYR1). Association analysis confirmed four known AIS single-nucleotide polymorphisms in our cohort. Gene set enrichment analysis revealed four gene clusters related to skeletal muscle contraction, extracellular matrix, and gene expression regulation. This WGS-based approach identified clinically relevant genetic variations and biological pathways in AIS patients, offering valuable insights into its complex development.

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.