NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson’s disease

Description

This paper introduces NERINE, a rare variant association test that links rare genetic variation with gene network topology to improve discovery power in complex diseases. Testing networks from canonical databases and model-system experiments, our method reveal disease-associated networks in biobanks. Together with CRISPRi screening in neuronal model, NERINE implicates an α-synuclein/prolactin stress-response in Parkinson’s disease. The experiments in CiS-CN and DA neuronal models in the context of Parkinson's disease were supported by ASAP.

Identifier (DOI)

10.1101/2025.01.07.631688

Discovery Team

Team Studer

Program

Collaborative Research Network

Theme

PD Functional Genomics

Meet the Authors

Sumaiya Nazeen

External Collaborator
Xinyuan Wang

External Collaborator
Lorenz Studer, MD

Lead PI (Core Leadership): Team Studer,

Memorial Sloan Kettering Cancer Center
Vikram Khurana, MD

Co-PI (Core Leadership): Team Studer,

Harvard University

NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson’s disease

Output Details

Meet the Authors

Sumaiya Nazeen

Xinyuan Wang

Lorenz Studer, MD

Vikram Khurana, MD

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