Deep Phenotyping at Scale: Study Protocol for the Korean Mood Disorder Genetic Study-Depression (KOMOGEN-D)

Area of Science:

• Psychiatry and Genetics
• Epidemiology
• Clinical Research Methodology

Background:

• Genetic analysis of major depressive disorder (MDD) is challenged by sample heterogeneity and diagnostic inaccuracies.
• Current genome-wide association studies (GWAS) often use self-reports or electronic health records, introducing biases.
• A need exists for large, well-characterized cohorts to explore genetic and environmental factors in MDD.

Purpose of the Study:

• To describe a novel methodology for recruiting and phenotyping large cohorts for genetic studies of MDD.
• To enhance sample homogeneity by focusing on specific patient subgroups.
• To overcome logistical challenges in large-scale clinical research.

Main Methods:

• Targeted ascertainment of cases through hospital-based recruitment.
• In-depth phenotyping using structured clinical interviews conducted by trained personnel.
• Recruitment of women with recurrent depressive episodes to increase sample homogeneity.
• Collaboration with 47 hospitals across South Korea, training 347 interviewers.

Main Results:

• Recruited 5704 cases and 4995 controls over 4 years, meeting significant recruitment targets.
• Confirmed cases exhibit recurrent, severe MDD with detailed clinical features.
• Successfully navigated challenges including COVID-19 restrictions and medical crises.
• Developed a scalable deep phenotyping strategy for MDD genetic research.

Conclusions:

• The described methodology yields deeply phenotyped, homogeneous cohorts suitable for genetic analysis of MDD.
• This approach can identify genetic influences on specific MDD subtypes and clinical features.
• The study design is adaptable for international collaboration to build larger MDD genetic research cohorts.