Can Psychiatric Genetics Advance Without Incorporating a Life Course Perspective?

Area of Science:

• Psychiatric Genetics
• Lifecourse Epidemiology
• Genomic Medicine

Background:

• Current genomic studies of psychiatric disorders primarily use single time-point data, often missing genetic variants relevant to lifecourse trajectories.
• This limitation affects understanding of symptom trajectories, age-at-onset, treatment response, and comorbidity evolution.

Purpose of the Study:

• To advocate for and demonstrate the utility of incorporating a lifecourse perspective into psychiatric genetics.
• To reconcile the portability of polygenic scores across age groups using longitudinal genome-wide association studies (GWAS).
• To identify novel genomic signals associated with time-dependent psychiatric phenotypes.

Main Methods:

• Conducting longitudinal genome-wide association studies (GWAS) in age-diverse samples.
• Utilizing advances in longitudinal biobanks and analytic tools.
• Applying post-GWAS functional annotation resources and analytic approaches.

Main Results:

• Pioneering longitudinal GWAS in psychiatry have identified novel genomic signals linked to time-dependent phenotypes.
• These signals are distinct from those associated with lifetime diagnoses from cross-sectional studies.
• Genomic contributions to psychiatric disorders are increasingly understood as dynamic, age- and exposure-dependent processes.

Conclusions:

• Integrating temporality into psychiatric genetics at scale is achievable and essential for discovery.
• Longitudinal GWAS complement cross-sectional approaches, offering new biological and therapeutic insights.
• This approach promises to reveal novel biology and therapeutic opportunities for psychiatric conditions.