Transmission Disequilibrium Tests Based on Read Counts for Low-Coverage Next-Generation Sequence Data
DC Field | Value | Language |
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dc.contributor.author | Kim, Wonkuk | - |
dc.date.available | 2019-03-08T20:39:01Z | - |
dc.date.issued | 2015-09 | - |
dc.identifier.issn | 0001-5652 | - |
dc.identifier.issn | 1423-0062 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/11425 | - |
dc.description.abstract | The purpose of this paper is the introduction of new statistical methods for case-parent trio association studies based on the read counts that can be obtained from next-generation sequencing (NGS) experiments. This work focuses on the inclusion of low-coverage data into the case-parent trio design without genotype classification or imputation. Two different approaches are considered: (1) a likelihood-based approach implementing a 15-component parametric mixture model and (2) a model-free approach that applies non-parametric statistical methods to the ratios of the read counts to coverage. Simulation studies are conducted to evaluate the performances of the proposed tests. In addition, the non-centrality parameters of the mixture likelihood-based tests are derived to determine sample sizes and coverage for a NGS experimental design. As an example, the sample sizes to maintain specified powers of a published adolescent idiopathic scoliosis (AIS) study are presented. The simulation results show that the tests using the genotypes classified by the maximum Bayesian posterior probability have significantly inflated type I error rates for low-coverage data. The tests using the posterior probabilities instead of the classified genotypes show lower power than the proposed tests. Generally, power for the likelihood-based approach is higher than that for the non-parametric ratio-based approach. For the AIS example, approximately 654 trios with 4x coverage are necessary to maintain 90% power when detecting an association of odds ratio 2 at a locus with a minor allele frequency of 0.35 at the level of significance alpha = 5 x 10(-8). By comparison, approximately 416 trios with 25x coverage are required to maintain the same power with the same settings. The R and C source codes to calculate the proposed test statistics, the sample sizes and power can be obtained by contacting the author (wkim@cau.ac.kr). (C) 2015 S. Karger AG, Basel | - |
dc.format.extent | 14 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | KARGER | - |
dc.title | Transmission Disequilibrium Tests Based on Read Counts for Low-Coverage Next-Generation Sequence Data | - |
dc.type | Article | - |
dc.identifier.doi | 10.1159/000434645 | - |
dc.identifier.bibliographicCitation | HUMAN HEREDITY, v.80, no.1, pp 36 - 49 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000362479400004 | - |
dc.identifier.scopusid | 2-s2.0-84939534418 | - |
dc.citation.endPage | 49 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 36 | - |
dc.citation.title | HUMAN HEREDITY | - |
dc.citation.volume | 80 | - |
dc.type.docType | Article | - |
dc.publisher.location | 스위스 | - |
dc.subject.keywordAuthor | EM algorithm | - |
dc.subject.keywordAuthor | Family-based association | - |
dc.subject.keywordAuthor | Likelihood ratio test | - |
dc.subject.keywordAuthor | Mixture model | - |
dc.subject.keywordAuthor | Non-centrality parameter | - |
dc.subject.keywordPlus | FAMILY-BASED ASSOCIATION | - |
dc.subject.keywordPlus | QUANTITATIVE-TRAIT LOCI | - |
dc.subject.keywordPlus | LINKAGE-DISEQUILIBRIUM | - |
dc.subject.keywordPlus | GENOTYPING ERRORS | - |
dc.subject.keywordPlus | TRANSMISSION/DISEQUILIBRIUM TEST | - |
dc.subject.keywordPlus | GENOME ASSOCIATION | - |
dc.subject.keywordPlus | COMPLEX DISEASES | - |
dc.subject.keywordPlus | RARE VARIANTS | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | GENES | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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