{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:43:31Z","timestamp":1772120611588,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T00:00:00Z","timestamp":1500595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R00HG008175"],"award-info":[{"award-number":["R00HG008175"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01HG008802"],"award-info":[{"award-number":["R01HG008802"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01HG007078"],"award-info":[{"award-number":["R01HG007078"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01GM114612"],"award-info":[{"award-number":["R01GM114612"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01GM118574"],"award-info":[{"award-number":["R01GM118574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01GM118609"],"award-info":[{"award-number":["R01GM118609"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U01EB023685"],"award-info":[{"award-number":["U01EB023685"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U54HL108460"],"award-info":[{"award-number":["U54HL108460"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000092","name":"NLM","doi-asserted-by":"publisher","award":["R00LM011392"],"award-info":[{"award-number":["R00LM011392"]}],"id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000092","name":"NLM","doi-asserted-by":"publisher","award":["R21LM012060"],"award-info":[{"award-number":["R21LM012060"]}],"id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>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\u2013control 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 \u2018re-identification\u2019 stays below a pre-specified risk threshold. \u2018Re-identification\u2019 in this context means that an attacker can infer that the presence of a family in a study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The software dpTDT is available in https:\/\/github.com\/mwgrassgreen\/dpTDT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx470","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T08:10:32Z","timestamp":1500538232000},"page":"3716-3725","source":"Crossref","is-referenced-by-count":24,"title":["Mechanisms to protect the privacy of families when using the transmission disequilibrium test in genome-wide association studies"],"prefix":"10.1093","volume":"33","author":[{"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Genetics, Stanford University, Stanford, CA, USA"}]},{"given":"Zhanglong","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, UC San Diego, La Jolla, CA, USA"}]},{"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, UC San Diego, La Jolla, CA, USA"}]},{"given":"Jihoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, UC San Diego, La Jolla, CA, USA"}]},{"given":"Hai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, UC San Diego, La Jolla, CA, USA"}]},{"given":"Xiaoqian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, UC San Diego, La Jolla, CA, USA"}]},{"given":"Lucila","family":"Ohno-Machado","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, UC San Diego, La Jolla, CA, USA"}]}],"member":"286","published-online":{"date-parts":[[2017,7,21]]},"reference":[{"key":"2023020207005359400_btx470-B1"},{"key":"2023020207005359400_btx470-B151","first-page":"503","author":"Bhaskar","year":"2010"},{"key":"2023020207005359400_btx470-B2","first-page":"btw758.","article-title":"PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS","author":"Chen","year":"2017","journal-title":"Bioinformatics"},{"key":"2023020207005359400_btx470-B3","doi-asserted-by":"crossref","DOI":"10.1038\/msb4100040","article-title":"The Personal Genome Project","volume":"1","author":"Church","year":"2005","journal-title":"Mol. 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In: Presidential Committee for the Study of Bioethical 2012."},{"key":"2023020207005359400_btx470-B13","doi-asserted-by":"crossref","first-page":"e1000167","DOI":"10.1371\/journal.pgen.1000167","article-title":"Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays","volume":"4","author":"Homer","year":"2008","journal-title":"PLoS Genet"},{"key":"2023020207005359400_btx470-B14","author":"Humbert","year":"2013"},{"key":"2023020207005359400_btx470-B15","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1038\/ng.455","article-title":"A new statistic and its power to infer membership in a genome-wide association study using genotype frequencies","volume":"41","author":"Jacobs","year":"2009","journal-title":"Nat. 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