Mount Sinai Careers

POSTDOCTORAL FELLOW

New York, New York
Research


Job Description

Postdoctoral Position – the Functional Convergence of Genetic Risk 

A postdoctoral position is available in the O’Reilly Lab, with a focus on the Functional Convergence of Genetic Risk. 

Polygenic models of disease typically assume additivity of risk variants, yet gene network and functional analyses indicate enrichment of signal across specific pathways for different traits. A key question is, thus, whether individual risk is due to the burden of risk across specific pathways or is instead merely due to the total additive burden across all identified risk variants. The former would imply high order interactions and the need to replace the ‘liability threshold’ model of disease with a ‘multiple liabilities’ model. This could lead to new ways to analyse genetic data, predict disease and stratify cases of disease. Projects will include, but are not be restricted to: 

- Investigation of evidence for functional convergence, exploiting the PRSet algorithm and software

- Stratify individuals with a heterogenous disease into more homogenous subsets according to differential gene-set based polygenic risk

- Explicitly test for high order interactions across highly convergent pathways and evaluate their impact on standard analyses (eg. heritability estimation, PRS)

Specific job duties

- Develop the PRSice/PRSet software to maintain their high flexibility and user-friendliness 
- Perform analyses and method developed as outlined in the above summary and as generated in conjunction with Dr O’Reilly
- Present findings at conferences and departmental meetings and write-up results as articles for publication
- Assist and share expertise with those in the lab and broader Mount Sinai research community


Postdoctoral Position – the Functional Convergence of Genetic Risk 

A postdoctoral position is available in the O’Reilly Lab, with a focus on the Functional Convergence of Genetic Risk. 

Polygenic models of disease typically assume additivity of risk variants, yet gene network and functional analyses indicate enrichment of signal across specific pathways for different traits. A key question is, thus, whether individual risk is due to the burden of risk across specific pathways or is instead merely due to the total additive burden across all identified risk variants. The former would imply high order interactions and the need to replace the ‘liability threshold’ model of disease with a ‘multiple liabilities’ model. This could lead to new ways to analyse genetic data, predict disease and stratify cases of disease. Projects will include, but are not be restricted to: 

- Investigation of evidence for functional convergence, exploiting the PRSet algorithm and software

- Stratify individuals with a heterogenous disease into more homogenous subsets according to differential gene-set based polygenic risk

- Explicitly test for high order interactions across highly convergent pathways and evaluate their impact on standard analyses (eg. heritability estimation, PRS)

Specific job duties

- Develop the PRSice/PRSet software to maintain their high flexibility and user-friendliness 
- Perform analyses and method developed as outlined in the above summary and as generated in conjunction with Dr O’Reilly
- Present findings at conferences and departmental meetings and write-up results as articles for publication
- Assist and share expertise with those in the lab and broader Mount Sinai research community

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