Curating the Clinical Genome 2024 ePoster Gallery-Secondary Findings Analysis in the Personalized Environment and Genes Study Reduced Return in Disorders with Autosomal Recessive Inheritance Pattern

Secondary Findings Analysis in the Personalized Environment and Genes Study Reduced Return in Disorders with Autosomal Recessive Inheritance Pattern

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The research conducted by the National Institute of Environmental Health Sciences aimed to analyze the interaction between genetic variants and the environment by enrolling participants in The Personalized Environment and Genes Study (PEGS). Genome sequencing was performed on 4,737 participants, with 97.9% consenting to receive secondary findings. Variants in specific genes were analyzed for potential return, with a focus on coding sequences and splice sites. A total of 3,151 variants remained after filtering, and 171 were classified as pathogenic or likely pathogenic for diseases suitable for secondary findings return.<br /><br />Interestingly, only 2.3% of participants had variants eligible for return as secondary findings, slightly lower than in similar studies. Various methods, including phone calls, letters, emails, and alternate contact sources, were utilized to reach participants. Of the identified variants, none were eligible for return based on autosomal recessive inheritance, while 87 variants in genes associated with autosomal dominant inheritance were deemed fit for return.<br /><br />The study found that participants showed high interest in receiving secondary findings during genome sequencing consent. The return of results was completed for 51% of participants who continued to consent. The research highlights the importance of considering ClinVar classifications in the filtering process while being cautious of over-filtering variants from underrepresented populations. Overall, the study sheds light on the complexities of returning secondary genetic findings and the varying impacts on participant engagement based on different inheritance patterns and disease associations.

Keywords

National Institute of Environmental Health Sciences

Personalized Environment and Genes Study

Genome sequencing

Secondary findings

Genetic variants

Pathogenic variants

Autosomal dominant inheritance

ClinVar classifications

Participant engagement

Underrepresented populations