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Secure and federated quantitative trait loci mapping with privateQTL
Columbia University, Department of Biomedical Informatics, New York, NY, USA; New York Genome Center, New York, NY, USA.
New York Genome Center, New York, NY, USA.
Brown University, Department of Computer Science, Providence, RI, USA.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. New York Genome Center, New York, NY, USA.ORCID iD: 0000-0002-7746-8109
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2025 (English)In: Cell Genomics, E-ISSN 2666-979X, Vol. 5, no 2, article id 100769Article in journal (Refereed) Published
Abstract [en]

Understanding the relationship between genotypes and phenotypes is crucial for advancing personalized medicine. Expression quantitative trait loci (eQTL) mapping plays a significant role by correlating genetic variants to gene expression levels. Despite the progress made by large-scale projects, eQTL mapping still faces challenges in statistical power and privacy concerns. Multi-site studies can increase sample sizes but are hindered by privacy issues. We present privateQTL, a novel framework leveraging secure multi-party computation for secure and federated eQTL mapping. When tested in a real-world scenario with data from different studies, privateQTL outperformed meta-analysis by accurately correcting for covariates and batch effect and retaining higher accuracy and precision for both eGene-eVariant mapping and effect size estimation. In addition, privateQTL is modular and scalable, making it adaptable for other molecular phenotypes and large-scale studies. Our results indicate that privateQTL is a practical solution for privacy-preserving collaborative eQTL mapping.

Place, publisher, year, edition, pages
Elsevier BV , 2025. Vol. 5, no 2, article id 100769
Keywords [en]
eQTL mapping, genomic privacy, multi-party computation, security
National Category
Computer Sciences Medical Genetics and Genomics
Identifiers
URN: urn:nbn:se:kth:diva-360185DOI: 10.1016/j.xgen.2025.100769Scopus ID: 2-s2.0-85217079966OAI: oai:DiVA.org:kth-360185DiVA, id: diva2:1938802
Note

QC 20250221

Available from: 2025-02-19 Created: 2025-02-19 Last updated: 2025-02-21Bibliographically approved

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Lappalainen, Tuuli

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