Skin of color dermatology is a growing field that is gaining more attention as the U.S. population diversifies. While there’s an understanding that some skin conditions are more prevalent in certain racial and ethnic groups, there’s little understanding as to why. In addition, self-reported race and ethnicity is not a fail-safe way of understanding a person’s skin. People are often multiracial or multiethnic, yet they may self-report a race or ethnicity based on their physical features and other factors.
A poster presented at Skin of Color Update and titled “Peripheral Blood Nascent RNA Sequencing Reveals Ancestry-Linked Differential Gene Expression in Immune and Skin Disease Pathways” looked at genetic ancestry — DNA that’s inherited from a person’s ancestral groups — and the role it plays in certain skin diseases. The poster outlines how understanding differences related to ancestry-linked gene expression could lead to a better understanding of the pathogenesis of skin disease as well as influence precision medicine. I interviewed the poster’s presenting author, Emily Uh, BS, of the Norton College of Medicine, SUNY Upstate Medical University.
What motivated you to explore whether genetic ancestry differences are at play in skin disease?
Several years ago, I first joined the Kwak Lab at Cornell University under the mentorship of Dr. Hojoong Kwak. Since then, I have had the privilege of working closely with my colleague and co-author Aileen Kimm, whose thesis demonstrated that genetic ancestry can offer a more accurate framework than race for interpreting gene expression patterns. Her work deeply shaped my interest in understanding whether similar ancestry-linked biological differences might contribute to skin disease mechanisms.
In dermatology, we often use the term skin of color to describe phenotypic differences, but this terminology does not necessarily reflect underlying genetic structure. As an aspiring dermatologist committed to equitable precision medicine, I began to ask whether ancestry-linked patterns could help us better understand genetic and immune variation in skin disease. That curiosity, grounded in several years of mentorship and research experience, ultimately motivated this study.
Epidemiological studies show that some skin diseases are more prevalent in certain ethnic groups. What do we know and not know about genetic ancestry and skin disease? What does your study add?
Although many dermatologic conditions vary in prevalence across ethnic groups, we know very little about the extent to which genetic ancestry contributes to these differences. Most studies rely on self-identified race or ethnicity, which capture sociocultural experience but not necessarily inherited genomic variation. As a result, biologically relevant population differences remain understudied.
Our work provides a new tool to explore these questions. Using nascent RNA sequencing, we demonstrated that genetic ancestry can be inferred directly from transcriptional data. In doing so, we identified robust ancestry-associated differences in gene expression, including genes with direct relevance to dermatology. For example, IFNGR2, a gene implicated in lichen planus, was more highly expressed in individuals with predominantly African Ancestry in Southwest United States (ASW) signatures, aligning with epidemiologic patterns. These findings underscore the potential of ancestry-informed analyses to deepen our biological understanding of population differences in skin disease.
How did you conduct your study, and what did you discover?
We analyzed 50 peripheral blood samples using chromatin run-on sequencing (pChRO). Because nascent RNA retains inherited genetic markers, we were able to identify ancestry-informative variants and infer both local and global ancestry using Bayesian approaches and 1000 Genomes Project reference populations.
One of our key findings was that genetic ancestry was a significantly stronger predictor of differential gene expression than self-identified race. When individuals were grouped by genetically inferred ancestry, more than 8 percent of highly expressed genes showed significant differential expression. The scale of these transcriptional differences, observed even in healthy individuals, was particularly striking. This suggests that baseline immune and epithelial regulatory programs may vary across ancestry groups in ways that could influence disease susceptibility, severity, and treatment response. We also observed an enrichment of dermatologically relevant transcriptional variation with more than 19 percent of skin-related genes showing differential expression. Together, these findings highlight the value of ancestry-informed approaches for advancing biological insight in skin disease research.
Did any of your findings surprise you?
Yes, we identified two individuals whose self-identified race did not match their genetically inferred ancestry. One participant who identified as Hispanic or Latino clustered with predominantly African Ancestry in Southwest United States (ASW), and another who identified as African American clustered more closely with Mexican Ancestry in Los Angeles (MXL). These mismatches may reflect vendor labeling errors, but they also illustrate the ambiguity of self-identification categories, particularly in older census formats where race and ethnicity were separated. This reinforces the limitations of race-based data in genomic and clinical research.
How could findings from this and subsequent studies transform patient care?
If ancestry-linked differences in immune and epithelial gene expression influence susceptibility to inflammatory or epidermal disorders, these insights may guide more targeted therapies and refine precision dermatology. Several genes that differed between ancestry groups in our study, such as IFNGR2 and LAMB3, play important roles in conditions including lichen planus, epidermolysis bullosa, and cutaneous squamous cell carcinoma.
Our next step is to analyze stimulated blood samples, including lipopolysaccharide-induced immune activation, to assess whether inflammatory responses also vary by ancestry. Ultimately, integrating genetic ancestry with clinical assessment has the potential to help dermatologists refine risk stratification, anticipate disease trajectories, and better tailor treatment for diverse patient populations.
Is there anything else dermatology clinicians should know about genetic ancestry differences and skin disease?
Genetic ancestry should not replace the clinical exam or the essential understanding of how social and structural factors influence patient health. However, it can serve as a valuable tool by providing insight into genetic variation that is not captured by race-based classifications. When used thoughtfully and interpreted within the appropriate scientific and social context, ancestry-informed analyses can deepen our understanding of population-level variation in skin disease and support more equitable approaches to precision dermatology.
Additional authors of the poster include:
Aileen Kimm, BA, Cornell University
Hojoong Kwak, MD, PhD, New York Medical College
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