NeuroGenConnect: Understanding Neuroticism by Integrating Genetics with Structural Brain Network Connectivity

• Applicants: Professorin Dr. Kirsten Hilger; Professor Dr. Sebastian Markett
• Subject Area: Biological Psychology and Cognitive Neuroscience ; Personality Psychology, Clinical and Medical Psychology, Methodology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557721320

Neuroticism is a key personality trait with significant public health implications, as elevated levels of neuroticism are linked to a higher risk for mental disorders, physical diseases, and variations in mortality and longevity. While neurobiological research has identified various brain characteristics associated with neuroticism and considerable progress has been made in understanding its molecular genetic foundation, a comprehensive framework that connects genetics, brain structure, and neuroticism is still lacking. The here proposed research project aims to address this gap by adopting an integrative approach that combines machine learning, network neuroscience and molecular genetics to further our understanding of individual differences in neuroticism. Both applicants will leverage their complementary experience to achieve three primary research goals: (1) Identifying a robust biomarker of neuroticism based on structural brain connectivity, (2) uncovering novel genetic markers and biological pathways associated with structural brain connectivity, and (3) examining whether the identified structural brain connectivity characteristics mediate the relationship between genetic factors and neuroticism. To move beyond previous studies, which were often non-reproducible, we will enhance replicability by utilizing data from two large open study samples (Human Connectome Project, UK-Biobank), by implementing multiple forms of cross-validation and by replicating all analyses in independent datasets. To address the challenge of deriving causal insights from correlative research on individual differences, we will employ Mendelian randomization, an approach that uses genetic variants as natural experiments to infer potential causal links between brain structure and neuroticism, thereby offering stronger evidence than traditional correlation-based methods. Strictly following Open Science practices, both applicants will ensure the preregistration of each study and the free distribution of all developed analysis code. Ultimately, the results will be integrated with existing empirical findings into a new holistic model of neuroticism, providing the basis for the development of new treatment and intervention strategies for mental disorders.

• DFG Programme: Research Grants
• International Connection: USA
• Cooperation Partner: Professor Dr. Olaf Sporns