中国神经再生研究(英文版) ›› 2021, Vol. 21 ›› Issue (5): 1997-1998.doi: 10.4103/NRR.NRR-D-24-01604

• 观点:退行性病与再生 • 上一篇    下一篇

揭示肌萎缩侧索硬化症缺失遗传性:我们应该更多地关注拷贝数变异吗?

  

  • 出版日期:2026-05-15 发布日期:2025-08-22

Unraveling the missing heritability of amyotrophic lateral sclerosis: Should we focus more on copy number variations?

Maria Guarnaccia, Valentina La Cognata, Giulia Gentile, Giovanna Morello, Sebastiano Cavallaro*   

  1. Institute for Biomedical Research and Innovation, National Research Council, Catania, Italy
  • Online:2026-05-15 Published:2025-08-22
  • Contact: Sebastiano Cavallaro, MD, PhD, sebastiano.cavallaro@cnr.it.

摘要: https://orcid.org/0000-0001-7590-1792 (Sebastiano Cavallaro)

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord, leading to muscle weakness, paralysis, and respiratory failure (Morgan and Orrell, 2016). Despite identifying many genes associated with ALS risk and pathogenesis, a discrepancy exists between heritability estimates based on familial studies (40%–60%) (Al-Chalabi et al., 2010) and heritability estimates derived from genetic data (5%–10%) (Megat et al., 2023), such as those obtained through GenomeWide Association Studies. This discrepancy, termed “missing heritability,” fuels ongoing debate and likely stems from ALS’s complex genetic architecture, limitations of current genetic research, unidentified genetic and epigenetic factors, environmental influences, random chance, and potential biases in family and twin study heritability estimates (Van Damme, 2018).