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<p>Although neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathophysiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here we performed a comprehensive analysis of genome-wide association study data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic signal and biological associations. Using complementary statistical tools, we demonstrate that a large set of common genetic variants impacts the risk of multiple neurological and psychiatric disorders, even in the absence of genetic correlations. Furthermore, genome-wide association studies on psychiatric disorders consistently implicate neuronal biology, whereas neurological diseases are associated with diverse neurobiological processes. Together, this study elucidates the genetic relationship between complex neurological and psychiatric disorders, indicating a larger degree of genetic pleiotropy than previously recognized. The findings have implications for disease classification, precision medicine and clinical practice.</p>

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A genome-wide analysis of the shared genetic risk architecture of complex neurological and psychiatric disorders

  • 期刊论文

  • 发表日期：

    2025年11月11日

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  • Olav B. Smeland,
  • Gleda Kutrolli,
  • Shahram Bahrami,
  • Vera Fominykh,
  • Nadine Parker,
  • Julian Fuhrer,
  • Guy F. L. Hindley,
  • Linn Rødevand,
  • Piotr Jaholkowski,
  • Markos Tesfaye,
  • Pravesh Parekh,
  • Torbjørn Elvsåshagen,
  • Andrew D. Grotzinger,
  • Nils Eiel Steen,
  • Dennis van der Meer,
  • Kevin S. O’Connell,
  • Srdjan Djurovic,
  • Anders M. Dale,
  • Alexey A. Shadrin,
  • Oleksandr Frei,
  • Ole A. Andreassen

摘要

Although neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathophysiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here we performed a comprehensive analysis of genome-wide association study data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic signal and biological associations. Using complementary statistical tools, we demonstrate that a large set of common genetic variants impacts the risk of multiple neurological and psychiatric disorders, even in the absence of genetic correlations. Furthermore, genome-wide association studies on psychiatric disorders consistently implicate neuronal biology, whereas neurological diseases are associated with diverse neurobiological processes. Together, this study elucidates the genetic relationship between complex neurological and psychiatric disorders, indicating a larger degree of genetic pleiotropy than previously recognized. The findings have implications for disease classification, precision medicine and clinical practice.