Genetic Architecture of Mental Disorders in Ancestrally Diverse Populations

Presenter:

Miri Gitik, Ph.D.
Division of Neuroscience and Basic Behavioral Science

Goal:

The goal of this initiative is to support the collection and genomic characterization of cohorts with severe mental illness from diverse ancestral backgrounds. The focus of this initiative would be the collection of large patient cohorts of non-Caucasian or admixed ancestries in the U.S. and around the globe. Study designs using case-control, parent-offspring trios, nuclear families or a combination thereof would be supported.

Rationale:

In the WHO Global Burden of Disease Study, active psychosis and severe depression were assigned to the most severe disability class along with quadriplegia and terminal stage cancer. Epidemiologic studies have shown that psychiatric diseases are found in every country and culture in the world. The global public health impact of severe mental illness cannot be overstated.

The success of personalized medicine depends on how well we understand genetic variation among ethnically diverse populations. To fully understand the biological mechanisms underlying disease and develop effective treatments for individuals of diverse ancestral background, genetic variation across the globe must be captured in research via expanding upon the data sets that inform genomic medicine and translating these findings into clinical care for all people equally.¹

To date, most genome wide genetic studies have focused on cohorts of European-ancestry for reasons such as population homogeneity and ease of ascertainment. While this has led to many successful genetic associations, the translation of these findings to other ancestries for risk prediction, (e.g., using polygenic risk scores), remains problematic. Therefore, studies of genetic variation in diverse populations are necessary to advance the important goal of global mental health discovery and equity.

The addition of genetic studies on diverse populations would not only promote treatment advances to populations worldwide and in the greatly admixed population within the United States, but would also contribute considerably to characterizing risk variants beyond what can be achieved with populations of European ancestry alone. Populations vary in terms of allele frequencies, biological adaptations and other properties that affect the detectability and importance of risk variants. No single ancestral population is sufficient for fully uncovering the risk variants underlying disease globally.²

References

¹ Ramos E, Callier SL, and Rotimi CN. Why personalized medicine will fail if we stay the course. Per Med. 2012 Nov; 9(8): 839–847.

² Rosenberg NA, Huang L, Jewett EM, Szpiech ZA, Jankovic I, and Boehnke M. Genome-wide association studies in diverse populations. Nat Rev Genet. 2010 May; 11(5): 356–366.