{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T03:22:21Z","timestamp":1722914541943},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"23","funder":[{"name":"NIH","award":["R01HG007508","U10CA180819"],"award-info":[{"award-number":["R01HG007508","U10CA180819"]}]},{"name":"the Hope Foundation"},{"name":"NIH","award":["R01GM117946"],"award-info":[{"award-number":["R01GM117946"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Motivation: Copy number variants (CNVs) have been implicated in a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability and schizophrenia. Recent advances in high-throughput genomic technologies have enabled rapid discovery of many genetic variants including CNVs. As a result, there is increasing interest in studying the role of CNVs in the etiology of many complex diseases. Despite the availability of an unprecedented wealth of CNV data, methods for testing association between CNVs and disease-related traits are still under-developed due to the low prevalence and complicated multi-scale features of CNVs.<\/jats:p>\n               <jats:p>Results: We propose a novel CNV kernel association test (CKAT) in this paper. To address the low prevalence, CNVs are first grouped into CNV regions (CNVR). Then, taking into account the multi-scale features of CNVs, we first design a single-CNV kernel which summarizes the similarity between two CNVs, and next aggregate the single-CNV kernel to a CNVR kernel which summarizes the similarity between two CNVRs. Finally, association between CNVR and disease-related traits is assessed by comparing the kernel-based similarity with the similarity in the trait using a score test for variance components in a random effect model. We illustrate the proposed CKAT using simulations and show that CKAT is more powerful than existing methods, while always being able to control the type I error. We also apply CKAT to a real dataset examining the association between CNV and autism spectrum disorders, which demonstrates the potential usefulness of the proposed method.<\/jats:p>\n               <jats:p>Availability and Implementation: A R package to implement the proposed CKAT method is available at http:\/\/works.bepress.com\/debashis_ghosh\/.<\/jats:p>\n               <jats:p>Contacts: \u00a0xzhan@fhcrc.org or debashis.ghosh@ucdenver.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw500","type":"journal-article","created":{"date-parts":[[2016,8,7]],"date-time":"2016-08-07T00:18:02Z","timestamp":1470529082000},"page":"3603-3610","source":"Crossref","is-referenced-by-count":14,"title":["A novel copy number variants kernel association test with application to autism spectrum disorders studies"],"prefix":"10.1093","volume":"32","author":[{"given":"Xiang","family":"Zhan","sequence":"first","affiliation":[{"name":"1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santhosh","family":"Girirajan","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA"},{"name":"3Department of Anthropology, Pennsylvania State University, University Park, PA 16802, USA and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Wu","sequence":"additional","affiliation":[{"name":"1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debashis","family":"Ghosh","sequence":"additional","affiliation":[{"name":"4Department of Biostatistics and Informatics, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,8,6]]},"reference":[{"key":"2023020114082041700_btw500-B1","volume-title":"Categorical Data Analysis","author":"Agresti","year":"2011"},{"key":"2023020114082041700_btw500-B2","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1038\/ng2028","article-title":"Methods and strategies for analyzing copy number variation using DNA microarrays","volume":"39","author":"Carter","year":"2007","journal-title":"Nat. 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