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In late October, the American Society for Human Genetics (ASHG) held its annual meeting was held (October 27-30, 2020), bringing together a global community of scientists, clinicians, and advocates to discuss the latest advances in human genetics and genomics research. While the pandemic circumstances made an in-person meeting impossible this year, the conference was successfully transitioned to an engaging and completely virtual online platform. Associate Editor Caitlin Moyer shares her experience at the virtual meeting this year.
The meeting began with ASHG President Anthony Wynshaw-Boris reflecting on the role that ASHG plays in advancing human genetics and genomics research. He drew upon inspiration from ASHG presidents who shepherded ASHG meetings in past challenging contexts in invoking the metaphor of the “big tent” – the notion that ASHG serves as a diverse and inclusive tent for the members of the broad genetics and genomics community in the US and internationally. The appropriateness of this description was apparent from the breadth and depth of new scientific discoveries, relevant social issues, and emerging technologies discussed. In particular, the concept of diversity emerged in many talks and discussions throughout the meeting, including examination of racial and ethnic disparities in disease risk and scrutinizing deficiencies in representation in genetic approaches to understand, prevent, and treat disease. The “big tent” metaphor was also illustrated by the vast number of presentations encompassing a wide range of cutting-edge techniques being developed and applied to questions in genetics and genomics research.
The need for increasing progress in promoting diversity in clinical genetics was touched on throughout the meeting, particularly during the Presidential Symposium, where Gary Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI) of the NIH, discussed existing disparities in disease among racial and ethnic groups and talked about what this means in terms of interactions between social and environmental factors and genetic contributions to disease. Noting the dramatic disparities between maternal mortality rates among Black and White women in the US, Dr. Gibbons highlighted how advancing genetic research affords an opportunity to address health disparities, for example, by helping to identify those at risk for cardiomyopathy, which exhibits a higher prevalence among African Americans. There is also a lot to be gained in terms of precision medicine, which could be leveraged to eliminate health disparities. To that effect, the Trans-Omics for Precision Medicine (TOPMed) program will apply cross-disciplinary expertise and technologies to gain insight into health disparities.
These sentiments were echoed in the “Asthma in Diverse Populations” session that was dedicated to understanding genetic and environmental contributions to asthma. Asthma exhibits disparity both in prevalence and mortality, both of which are disproportionately higher among Black and Puerto Rican populations in the US. Asthma is a polygenic disorder and improved tools are needed to understand how genetics contribute to risk, however existing tools such as polygenic risk scores, are disproportionately more accurately applied in European than non-European populations, as they’re developed based on genetic information from individuals of European ancestry. In her talk on genetic insights into asthma derived from studying diverse populations, Alicia Martin, a researcher at the Broad Institute, noted that Eurocentric studies are problematic not only in that they contribute to health disparities, but also because they can limit progress relevant for all.
Resources exist to study the relationships between genetics, environmental or lifestyle factors and disease, such as the UK Biobank, a longitudinal biobank study that initiated in 2006 in the UK. While biobanks provide a wealth of data to facilitate research on the genetic basis of disease, they are limited by a lack of diverse ancestry representation. Masahiro Kanai, a doctoral student at Harvard Medical School, spoke on work demonstrating how diversity can benefit fine mapping discovery of genetic variants underlying complex traits. In his talk, titled “Insights into fine-mapping causal variants of complex traits from diverse populations”, Kanai sought to address challenges in identifying causal variants, partly a result of an absence of large-scale GWAS from diverse populations. His research applied a cross-population approach, analyzing fine mapping results across three biobanks (Biobank Japan, UK Biobank and FinnGen). The analyses identified putative causal variants across a number of complex traits, demonstrating how diversity can benefit fine mapping discovery and inform our understanding of disease.
Methodological developments applied to genetic and genomic research were discussed throughout the meeting, including computational advances and machine learning techniques that can be used to advance human health, even in instances where genotyping data are lacking. In his talk, Douglas Shaw, a doctoral student at Vanderbilt University, described an approach using a phenome risk classification machine learning algorithm to identify patients at risk for developmental stuttering, a speech disorder affecting around 1% of the population. The model takes phecodes identified to be enriched in individuals with stuttering in Vanderbilt’s electronic health record (EHR) system for whom genotyping records are not available, and applies these as predictor variables in a unique model. When the model was used to identify stuttering cases among a set of genotyped cases selected for a preliminary GWAS, the findings led to the identification of a novel variant associated with developmental stuttering risk. The work highlights how machine learning techniques can be applied to expand how biobank data can be used to better understand the genetic contributions to stuttering.
Technological advancements and improvements in representativeness in genetics and genomics research are needed to address public health issues, and it is important to assess how these advances can be translated to promote community health. Broader application of genetic testing has the potential to increase our ability to predict and prevent disease, as noted by Amy Lemke, a researcher at University of Chicago and Program Director of Outcomes Research and Personalized Medicine at NorthShore University HealthSystem researching the impacts of new genomic technology for patients and the public. In her talk, Dr. Lemke described findings of a survey of primary care patients in the Chicago, IL area, who were offered genetic testing. The study was geared toward the assessment of patient perceptions and utilization of the results through discussions of the test results with healthcare providers. The talk illustrated how increased knowledge of patient attitudes regarding satisfaction with testing, understanding of the implications of the test results, and concerns over issues relating to privacy and discrimination issues is important to aid in understanding how genomic testing can best be implemented across many communities. Further work is needed to ensure that these increasingly available technologies can be used to universally benefit diverse communities.
These talks represent of only a fraction of the rich scientific and clinical discussions that took place, many of which described exciting technological advances, or touched on important aspects of promoting diversity in genetics and genomics. Even though the ASHG annual meeting “tent” was a virtual one this year, this did not stand in the way of a collaborative and cross-disciplinary meeting exemplifying the ASHG mission to promote advances in genetic and genomics medicine will be to the benefit of all.
Photo credit: Ri Butov, Pixabay