File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Detection of parent-of-origin effects in complete and incomplete nuclear families with multiple affected children using multiple tightly linked markers

TitleDetection of parent-of-origin effects in complete and incomplete nuclear families with multiple affected children using multiple tightly linked markers
Authors
KeywordsAssortative mating demographic model
Complete nuclear family
Haplotype analysis
Incomplete nuclear family
Missing parent
Multiple testing
Parent-of-origin effects
Population stratification demographic model
Single-marker analysis
Issue Date2009
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/HHE
Citation
Human Heredity, 2009, v. 67 n. 2, p. 116-127 How to Cite?
AbstractFor a diallelic marker locus, the parental-asymmetry test (PAT) based on case-parents trios and its extensions to accommodate incomplete unclear families (1-PAT and C-PAT) are simple and powerful approaches to test for parent-of-origin effects. However, haplotype analysis is generally regarded as advantageous over single-marker analysis in genetic study of common complex diseases. This is mainly due to the fact that complex diseases are often associated with multiple markers. As such, HAP-PAT was constructed to test for parent-of-origin effects in the framework of haplotype analysis. However, its applicability is limited due to the need for complete parental information. In this paper, for nuclear families with only one parent and multiple affected children, we develop HAP-1-PAT to test for parent-of-origin effects using multiple tightly linked markers. We further propose HAP-C-PAT to combine data from families with both parents and those with only one parent. We carry out a simulation study to evaluate the validity and power of the test statistics in various settings, including incomplete family rates, marker/disease-locus linkage disequilibrium patterns, and population models. We perform analysis for all possible combinations of the markers being considered. A permutation-based Monte Carlo procedure is devised to determine the significance of the tests; the corrected global p values taking into account of multiple testing are used for inferences. The results show that HAP-1-PAT and HAP-C-PAT would work well even under the population stratification demographic model and assortative mating demographic model. Furthermore, for the disease models considered, there are significant gains in power from haplotype analysis compared to single-marker analysis, and from combined analysis using HAP-C-PAT compared to analysis using HAP-PAT for the complete family data only. Copyright © 2008 S. Karger AG.
Persistent Identifierhttp://hdl.handle.net/10722/59851
ISSN
2015 Impact Factor: 1.539
2015 SCImago Journal Rankings: 0.942
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong RGC CERG ResearchHKU 702207P
National Natural Science Foundation of China10561008
National Institute of Health5R01HG002657
Funding Information:

We would like to thank an associate editor and two reviewers for their insightful and helpful suggestions which greatly improved our presentation. This work was partially supported by a Hong Kong RGC CERG Research Grant (HKU 702207P), the National Natural Science Foundation of China (10561008), and the National Institute of Health grant 5R01HG002657.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorZhou, JYen_HK
dc.contributor.authorLin, Sen_HK
dc.contributor.authorFung, WKen_HK
dc.contributor.authorHu, YQen_HK
dc.date.accessioned2010-05-31T03:58:46Z-
dc.date.available2010-05-31T03:58:46Z-
dc.date.issued2009en_HK
dc.identifier.citationHuman Heredity, 2009, v. 67 n. 2, p. 116-127en_HK
dc.identifier.issn0001-5652en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59851-
dc.description.abstractFor a diallelic marker locus, the parental-asymmetry test (PAT) based on case-parents trios and its extensions to accommodate incomplete unclear families (1-PAT and C-PAT) are simple and powerful approaches to test for parent-of-origin effects. However, haplotype analysis is generally regarded as advantageous over single-marker analysis in genetic study of common complex diseases. This is mainly due to the fact that complex diseases are often associated with multiple markers. As such, HAP-PAT was constructed to test for parent-of-origin effects in the framework of haplotype analysis. However, its applicability is limited due to the need for complete parental information. In this paper, for nuclear families with only one parent and multiple affected children, we develop HAP-1-PAT to test for parent-of-origin effects using multiple tightly linked markers. We further propose HAP-C-PAT to combine data from families with both parents and those with only one parent. We carry out a simulation study to evaluate the validity and power of the test statistics in various settings, including incomplete family rates, marker/disease-locus linkage disequilibrium patterns, and population models. We perform analysis for all possible combinations of the markers being considered. A permutation-based Monte Carlo procedure is devised to determine the significance of the tests; the corrected global p values taking into account of multiple testing are used for inferences. The results show that HAP-1-PAT and HAP-C-PAT would work well even under the population stratification demographic model and assortative mating demographic model. Furthermore, for the disease models considered, there are significant gains in power from haplotype analysis compared to single-marker analysis, and from combined analysis using HAP-C-PAT compared to analysis using HAP-PAT for the complete family data only. Copyright © 2008 S. Karger AG.en_HK
dc.languageengen_HK
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/HHEen_HK
dc.relation.ispartofHuman Heredityen_HK
dc.rightsHuman Heredity. Copyright © S Karger AG.en_HK
dc.subjectAssortative mating demographic modelen_HK
dc.subjectComplete nuclear familyen_HK
dc.subjectHaplotype analysisen_HK
dc.subjectIncomplete nuclear familyen_HK
dc.subjectMissing parenten_HK
dc.subjectMultiple testingen_HK
dc.subjectParent-of-origin effectsen_HK
dc.subjectPopulation stratification demographic modelen_HK
dc.subjectSingle-marker analysisen_HK
dc.titleDetection of parent-of-origin effects in complete and incomplete nuclear families with multiple affected children using multiple tightly linked markersen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0001-5652&volume=67&spage=116&epage=127&date=2009&atitle=Detection+of+parent-of-origin+effects+in+complete+and+incomplete+nuclear+families+with+multiple+affected+children+using+multiple+tightly+linked+markersen_HK
dc.identifier.emailFung, WK: wingfung@hku.hken_HK
dc.identifier.emailHu, YQ: yqhu@hku.hken_HK
dc.identifier.authorityFung, WK=rp00696en_HK
dc.identifier.authorityHu, YQ=rp00708en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1159/000179559en_HK
dc.identifier.pmid19077428-
dc.identifier.scopuseid_2-s2.0-57449096200en_HK
dc.identifier.hkuros158073en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57449096200&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume67en_HK
dc.identifier.issue2en_HK
dc.identifier.spage116en_HK
dc.identifier.epage127en_HK
dc.identifier.isiWOS:000262546300004-
dc.publisher.placeSwitzerlanden_HK
dc.relation.projectTransmission disequilibrium test under imprinting for quantitative traits based on case-parents trios and for qualitative traits when only one parent is available-
dc.identifier.scopusauthoridZhou, JY=16240300900en_HK
dc.identifier.scopusauthoridLin, S=7407613676en_HK
dc.identifier.scopusauthoridFung, WK=13310399400en_HK
dc.identifier.scopusauthoridHu, YQ=13410089000en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats