Background With direct-to-consumer (DTC) genetic testing enabling self-responsible access to novel information on ancestry, traits, or health, consumers often turn to social media for assistance and discussion. YouTube, the largest social media platform for videos, offers an abundance of DTC genetic testing–related videos. Nevertheless, user discourse in the comments sections of these videos is largely unexplored. Objective This study aims to address the lack of knowledge concerning user discourse in the comments sections of DTC genetic testing–related videos on YouTube by exploring topics discussed and users' attitudes toward these videos. Methods We employed a 3-step research approach. First, we collected metadata and comments of the 248 most viewed DTC genetic testing–related videos on YouTube. Second, we conducted topic modeling using word frequency analysis, bigram analysis, and structural topic modeling to identify topics discussed in the comments sections of those videos. Finally, we employed Bing (binary), National Research Council Canada (NRC) emotion, and 9-level sentiment analysis to identify users' attitudes toward these DTC genetic testing–related videos, as expressed in their comments. Results We collected 84,082 comments from the 248 most viewed DTC genetic testing–related YouTube videos. With topic modeling, we identified 6 prevailing topics on (1) general genetic testing, (2) ancestry testing, (3) relationship testing, (4) health and trait testing, (5) ethical concerns, and (6) YouTube video reaction. Further, our sentiment analysis indicates strong positive emotions (anticipation, joy, surprise, and trust) and a neutral-to-positive attitude toward DTC genetic testing–related videos. Conclusions With this study, we demonstrate how to identify users' attitudes on DTC genetic testing by examining topics and opinions based on YouTube video comments. Shedding light on user discourse on social media, our findings suggest that users are highly interested in DTC genetic testing and related social media content. Nonetheless, with this novel market constantly evolving, service providers, content providers, or regulatory authorities may still need to adapt their services to users' interests and desires.

BACKGROUND With direct-to-consumer (DTC) genetic testing allowing consumers self-responsible access to novel information on their ancestry, traits, or health, consumers often turn to social media for assistance and discussion. While YouTube, the largest social media platform for videos, offers an abundance of DTC genetic testing-related videos, user discourse in the comments sections of these videos is largely unexplored. OBJECTIVE This study aims to address the lack of knowledge concerning user discourse in the comments sections of DTC genetic testing-related videos on YouTube by exploring topics discussed and users’ attitudes toward these videos. METHODS We employed a 3-step research approach. First, we collected metadata and comments of the 248 most viewed DTC genetic testing-related videos on YouTube. Second, we conducted topic modeling utilizing word frequency analysis, bi-gram analysis, and structural topic modeling to identify topics discussed in the comment sections of those videos. Last, we employed Bing (binary), NRC emotion, and 9-level sentiment analysis to identify users’ attitudes toward these DTC genetic testing-related videos, as expressed in the comments. RESULTS We collected 84,082 comments from the 248 most viewed DTC genetic testing-related YouTube videos. With the topic modeling, we identified six prevailing topics on (1) general genetic testing, (2) ancestry testing, (3) relationship testing, (4) health and trait testing, (5) ethical concerns, and (6) YouTube video reaction. Further, our sentiment analysis indicates strong positive emotions (anticipation, joy, surprise, and trust) and a neutral to positive attitude toward DTC genetic testing-related videos. CONCLUSIONS With this study, we demonstrate how to identify users' attitudes on DTC genetic testing by examining topics and opinions based on YouTube video comments. Shedding light on user discourse in social media, our findings suggest that users are highly interested in DTC genetic testing and related social media content. Nonetheless, with this novel market constantly evolving, service providers, content providers, or regulatory authorities may still need to adapt their services to users’ interests and desires.