Scholarlink

<p>Epidemiological literature describes widespread psychiatric–physical comorbidity. However, the extent to which observed bivariate risk is transdiagnostic remains uncertain. We apply Genomic SEM and introduce Genomic E-SEM, an exploratory factor-analytic extension of Genomic SEM, here applied to 73 physical outcomes (~1.9 million cases) across eight medical domains. We then modeled latent physical illness factors alongside previously identified psychiatric factors. Thought/psychotic and compulsive factors exhibited few associations with physical illness factors. Conversely, internalizing, neurodevelopmental, and substance-use factors showed substantial genome-wide genetic correlations with all physical illness systems. Multivariate GWAS of a transdiagnostic physical illness factor, defined by 21 physical disorders, identified 27 genomic risk loci and exhibited substantial predictive validity in subsequent PheWAS. This transdiagnostic factor again exhibited substantial genome-wide genetic correlations with internalizing, neurodevelopmental, and substance-use factors. Our results reveal pervasive risk sharing between specific groups of psychiatric and physical conditions and suggest the need for additional nosological frameworks.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Shared Genetic Liability across Systems of Psychiatric and Physical Illness

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月21日

查看全文
  • Jeremy M. Lawrence,
  • Isabelle F. Foote,
  • Sophie Breunig,
  • Lukas S. Schaffer,
  • Siraj Lyons,
  • Sarah A. Abramowitz,
  • Michael G. Levin,
  • Scott M. Damrauer,
  • Travis T. Mallard,
  • Andrew D. Grotzinger

摘要

Epidemiological literature describes widespread psychiatric–physical comorbidity. However, the extent to which observed bivariate risk is transdiagnostic remains uncertain. We apply Genomic SEM and introduce Genomic E-SEM, an exploratory factor-analytic extension of Genomic SEM, here applied to 73 physical outcomes (~1.9 million cases) across eight medical domains. We then modeled latent physical illness factors alongside previously identified psychiatric factors. Thought/psychotic and compulsive factors exhibited few associations with physical illness factors. Conversely, internalizing, neurodevelopmental, and substance-use factors showed substantial genome-wide genetic correlations with all physical illness systems. Multivariate GWAS of a transdiagnostic physical illness factor, defined by 21 physical disorders, identified 27 genomic risk loci and exhibited substantial predictive validity in subsequent PheWAS. This transdiagnostic factor again exhibited substantial genome-wide genetic correlations with internalizing, neurodevelopmental, and substance-use factors. Our results reveal pervasive risk sharing between specific groups of psychiatric and physical conditions and suggest the need for additional nosological frameworks.