Welcome to the Penn Medicine Center for Genetics of Complex Disease.

Directed by Dr. Joan O’Brien, the Center seeks to elucidate the genetics of diseases that overaffect understudied populations, with an overall goal of developing personalized diagnostic and therapeutic strategies. Our initial focus is on African-ancestry populations. African ancestry individuals are severely under-represented in genetic research. This ancestry makes up only 2% of participants in genome-wide association studies (GWAS) as of 2019,¹ even for diseases where these patients are overaffected and the disease has a familial basis. This disparity not only limits understanding of disease biology, but also impedes the translation of findings into clinical action for underserved populations.² 

Dr. O’Brien recognized a health disparity in the familial eye disease of glaucoma, which is the leading cause of irreversible blindness worldwide.³ In 2014, she launched an ambitious study to elucidate the genetics of this disease in African ancestry individuals,⁴ who are five times more frequently and 15 times more severely affected by glaucoma than European Americans.^{5, 6} Today, the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study has enrolled more than 10,250 individuals from Philadelphia, making it the largest African ancestry cohort enrolled in a single city. 

This Center provides the resources needed to expand research efforts beyond glaucoma to other diseases with genetic components that remain understudied in Black individuals. Areas of interest include hypertension, heart disease, stroke, sickle cell disease, liver disease, and sarcoidosis, all of which overaffect individuals of African descent. The Center continues to emphasize close partnerships formed with community members and leaders during the POAAGG study to address health disparities, provide frequent disease screenings, and spread awareness of findings.

CENTER MISSION:

The Center aims to bring precision medicine approaches to understudied populations for robust disease screening, individualized therapeutics, and improved population health. More specifically, we have the following objectives at the Center:

1. Identify and investigate regions of interest for glaucoma in African ancestry individuals. 
2. Elucidate the genetic architecture of other diseases that disproportionately affect African ancestry individuals.
3. Translate genetic findings into personalized diagnostic and therapeutic strategies for glaucoma and other diseases in African ancestry populations.

References:

1. Sirugo, G., Williams, S. M. & Tishkoff, S. A. The Missing Diversity in Human Genetic Studies. Cell 177, 26-31 (2019).
2. Popejoy, A. & Fullerton, S. Genomics is failing on diversity. Nature 538, 161-164 (2016).
3. Quigley, H. A. & Broman, A. T. The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 90, 262-267 (2006).
4. Charlson, E. S. et al. The primary open-angle african american glaucoma genetics study: baseline demographics. Ophthalmology 122, 711-720 (2015).
5. Tielsch, J. M., Katz, J., Sommer, A., Quigley, H. A. & Javitt, J. C. Family history and risk of primary open angle glaucoma. The Baltimore Eye Survey. Arch. Ophthalmol. 112, 69-73 (1994).
6. Munoz, B. et al. Causes of blindness and visual impairment in a population of older Americans: The Salisbury Eye Evaluation Study. Arch. Ophthalmol. 118, 819-825 (2000).