Moving Beyond 'One Gene, One Disease': Embracing Genetic Complexity for Personalized Medicine

Genetic inheritance has traditionally been viewed through the lens of the simple one gene-one trait or disease paradigm. In clinical practice, genetics is often utilized to identify specific disease-causing genes, aiding in diagnosis and treatment. However, emerging research reveals that the relationship between genes and health conditions is far more intricate than previously thought.

Your DNA harbors millions of genetic variants, inherited or randomly arising, that influence a wide range of traits and health issues. These variants include common ones shared across populations and rare or unique mutations found in specific families. Recent studies published in the journal Cell highlight that conditions like autism and schizophrenia are affected not just by single mutations but by complex interactions involving multiple genetic variants.

The concept of primary and secondary variants helps explain the variability in disease manifestation. Primary variants are the main mutations that can directly cause disease, such as those responsible for sickle cell anemia or cystic fibrosis. Secondary variants, meanwhile, can modulate how a primary mutation influences disease development and severity. These secondary genetic factors can amplify or mitigate symptoms, leading to differences in severity and manifestation even among individuals with the same primary mutation.

An example involves research on a specific chromosome deletion known as 16p12.1 deletion. This mutation is linked to developmental delays and psychiatric disorders. However, the severity and range of symptoms depend significantly on additional secondary variants inherited from both parents. These secondary variants can be associated with various traits like smaller head size or greater cognitive impairment, illustrating how multiple genetic factors interact to shape health outcomes.

Furthermore, bias in genetic research—such as recruitment focus on individuals with severe symptoms—may obscure the full picture of genetic influence. Broader population studies reveal that many individuals carry these variants with milder or no symptoms, underscoring the importance of diverse data in understanding genetic risks.

The emerging consensus advocates for a paradigm shift: moving away from a deterministic model toward one that considers the dynamic interaction between multiple genetic variants and environmental influences. This approach enables clinicians to better predict disease risk and progression, facilitating personalized treatment and counseling.

As research advances, incorporating comprehensive genetic profiles into medical practice promises more accurate prognosis, tailored therapies, and improved disease prevention strategies. Embracing the complexity of human genetics is crucial for realizing the full potential of personalized medicine.

Source: https://medicalxpress.com/news/2025-10-gene-disease-acknowledging-full-complexity.html