Figure. Inherited threshold model of disease describes how common modifiers may influence rare monogenic diseases (Klasfeld et al 2014, Kingdom &Wright 2022)

Summary:

• Organized genetic and medical data leveraged from self-reports, electronic health records, and ~500K exomes in the UK biobank and generated version-controlled code with git to ensure reproducibility

• Leveraged latest update of UK biobank to identify a sufficiently sized cohort of known and novel cardiomyopathy variant carriers to improve upon previous studies without adequate statistical power

• Calculated PRS from relevant GWAS and evaluated logistic, cox, and linear regression to quantify the association of common variants on disease penetrance, onset, and severity among the rare pathogenic variant carriers and use the results to provide genetic insight for decreasing disease outcomes

• Articulated technical genetic study in internal symposiums to showcase my work to multidisciplinary audiences including nonsubject matter experts (eg. biologists, leadership)

Publications

Klasfeld, S. J., Knutson, K. A., Miller, M. R., Fauman, E., Berghout, J., Moccia, R., & Kim, H. I. (2024). Common genetic modifiers influence cardiomyopathy susceptibility among the carriers of rare pathogenic variants. medRxiv.

Presentations

• Klasfeld, S., Fauman, E.B., Miller, M.R., Moccia, R., & Kim, H.I. (2024, November 5). Coding cis pQTLs from proteogenomic data allow evaluation of the performance of missense variant effect predictions and the utility of their application to rare variant association analyses. [Poster]. American Society of Human Genetics, Denver, CO.

• Klasfeld, S., Moccia, R., Knutson, A., Berghout, J., & Kim, H.I. (2023, November 1). Common genetic modifiers influence disease risk in carriers of rare pathogenic cardiomyopathy variants [Poster]. Pfizer Worldwide Research, Development and Medical Postdoc Symposium, Cambridge, MA.

• Klasfeld, S., Moccia, R., Knutson, A., Berghout, J., & Kim, H.I. (2023, November 2). Genetic modifiers illuminate clinical phenotype penetrance in carriers of rare cardiomyopathy-causal variants [PowerPoint slides]. Pfizer Worldwide Research, Development and Medical Postdoc Symposium, Cambridge, MA.

• Klasfeld, S., Moccia, R., & Berghout, J. (2022, November 2). Genetic modifiers illuminate frequency and penetrance of clinical and subclinical phenotypes in carriers of rare cardiomyopathy-causal variants [Poster]. Pfizer Worldwide Research, Development and Medical Postdoc Symposium, Cambridge, MA.