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Bioinformatics. 2017 Dec 1;33(23):3716-3725. doi: 10.1093/bioinformatics/btx470.

Mechanisms to protect the privacy of families when using the transmission disequilibrium test in genome-wide association studies.

Author information

Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Department of Biomedical Informatics, UC San Diego, La Jolla, CA 92093, USA.



Inappropriate disclosure of human genomes may put the privacy of study subjects and of their family members at risk. Existing privacy-preserving mechanisms for Genome-Wide Association Studies (GWAS) mainly focus on protecting individual information in case-control studies. Protecting privacy in family-based studies is more difficult. The transmission disequilibrium test (TDT) is a powerful family-based association test employed in many rare disease studies. It gathers information about families (most frequently involving parents, affected children and their siblings). It is important to develop privacy-preserving approaches to disclose TDT statistics with a guarantee that the risk of family 're-identification' stays below a pre-specified risk threshold. 'Re-identification' in this context means that an attacker can infer that the presence of a family in a study.


In the context of protecting family-level privacy, we developed and evaluated a suite of differentially private (DP) mechanisms for TDT. They include Laplace mechanisms based on the TDT test statistic, P-values, projected P-values and exponential mechanisms based on the TDT test statistic and the shortest Hamming distance (SHD) score.


Using simulation studies with a small cohort and a large one, we showed that that the exponential mechanism based on the SHD score preserves the highest utility and privacy among all proposed DP methods. We provide a guideline on applying our DP TDT in a real dataset in analyzing Kawasaki disease with 187 families and 906 SNPs. There are some limitations, including: (1) the performance of our implementation is slow for real-time results generation and (2) handling missing data is still challenging.

Availability and implementation:

The software dpTDT is available in


Supplementary information:

Supplementary data are available at Bioinformatics online.

[Indexed for MEDLINE]
Free PMC Article

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