Genetic disease risks of under-represented founder populations in New York City.

The detection of founder pathogenic variants, those observed in high frequency only in a group of individuals with increased inter-relatedness, can help improve delivery of health care for that community. We identified 16 groups with shared ancestry, based on genomic segments that are shared through identity by descent (IBD), in New York City using the genomic data of 25,366 residents from the All Of Us Research Program and the Mount Sinai Bio It is well recognized that genomic studies have been biased towards individuals of European ancestry, and that obtaining medical insights for populations under-represented in medical genomics is crucial to achieve health equity. Here, we use genomic information to identify networks of individuals in New York City who are distinctively related to each other, allowing us to define populations with common genetic ancestry based on genetic similarities rather than by self-reported race or ethnicity. In our study of >25,000 New Yorkers, we identified eight highly-interrelated founder populations, with 202 likely disease-causing variants with increased frequencies in specific founder populations. Many of these population-specific variants are new discoveries, despite their high frequency in founder populations. Studying recent genetic ancestry can help reveal population-specific disease insights that can help with early diagnosis, carrier screening, and opportunities for targeted therapies that all help to reduce health disparities in genomic medicine.