File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Evaluating the heritability explained by known susceptibility variants: A survey of ten complex diseases

TitleEvaluating the heritability explained by known susceptibility variants: A survey of ten complex diseases
Authors
KeywordsAssociation study
Genetic architecture
Liability threshold model
Variance explained
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35841
Citation
Genetic Epidemiology, 2011, v. 35 n. 5, p. 310-317 How to Cite?
AbstractRecently, an increasing number of susceptibility variants have been identified for complex diseases. At the same time, the concern of "missing heritability" has also emerged. There is however no unified way to assess the heritability explained by individual genetic variants for binary outcomes. A systemic and quantitative assessment of the degree of "missing heritability" for complex diseases is lacking. In this study, we measure the variance in liability explained by individual variants, which can be directly interpreted as the locus-specific heritability. The method is extended to deal with haplotypes, multi-allelic markers, multi-locus genotypes, and markers in linkage disequilibrium. Methods to estimate the standard error and confidence interval are proposed. To assess our current level of understanding of the genetic basis of complex diseases, we conducted a survey of 10 diseases, evaluating the total variance explained by the known variants. The diseases under evaluation included Alzheimer's disease, bipolar disorder, breast cancer, coronary artery disease, Crohn's disease, prostate cancer, schizophrenia, systemic lupus erythematosus (SLE), type 1 diabetes and type 2 diabetes. The median total variance explained across the 10 diseases was 9.81%, while the median variance explained per associated SNP was around 0.25%. Our results suggest that a substantial proportion of heritability remains unexplained for the diseases under study. Programs to implement the methodologies described in this paper are available at. © 2011 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/135439
ISSN
2015 Impact Factor: 2.553
2015 SCImago Journal Rankings: 2.101
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 766906M
HKU 774707M
University of Hong Kong Strategic Research Theme of Genomics
Croucher Foundation
Funding Information:

Contract grant sponsor: Hong Kong Research Grants Council General Research Fund; Contract grant numbers: HKU 766906M; HKU 774707M; Contract grant sponsors: University of Hong Kong Strategic Research Theme of Genomics; Croucher Foundation Scholarship.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorSo, HCen_HK
dc.contributor.authorGui, AHen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorSham, PCen_HK
dc.date.accessioned2011-07-27T01:35:10Z-
dc.date.available2011-07-27T01:35:10Z-
dc.date.issued2011en_HK
dc.identifier.citationGenetic Epidemiology, 2011, v. 35 n. 5, p. 310-317en_HK
dc.identifier.issn0741-0395en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135439-
dc.description.abstractRecently, an increasing number of susceptibility variants have been identified for complex diseases. At the same time, the concern of "missing heritability" has also emerged. There is however no unified way to assess the heritability explained by individual genetic variants for binary outcomes. A systemic and quantitative assessment of the degree of "missing heritability" for complex diseases is lacking. In this study, we measure the variance in liability explained by individual variants, which can be directly interpreted as the locus-specific heritability. The method is extended to deal with haplotypes, multi-allelic markers, multi-locus genotypes, and markers in linkage disequilibrium. Methods to estimate the standard error and confidence interval are proposed. To assess our current level of understanding of the genetic basis of complex diseases, we conducted a survey of 10 diseases, evaluating the total variance explained by the known variants. The diseases under evaluation included Alzheimer's disease, bipolar disorder, breast cancer, coronary artery disease, Crohn's disease, prostate cancer, schizophrenia, systemic lupus erythematosus (SLE), type 1 diabetes and type 2 diabetes. The median total variance explained across the 10 diseases was 9.81%, while the median variance explained per associated SNP was around 0.25%. Our results suggest that a substantial proportion of heritability remains unexplained for the diseases under study. Programs to implement the methodologies described in this paper are available at. © 2011 Wiley-Liss, Inc.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35841en_HK
dc.relation.ispartofGenetic Epidemiologyen_HK
dc.rightsGenetic Epidemiology. Copyright © John Wiley & Sons, Inc.-
dc.subjectAssociation studyen_HK
dc.subjectGenetic architectureen_HK
dc.subjectLiability threshold modelen_HK
dc.subjectVariance explaineden_HK
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenetic Variation-
dc.subject.meshGenome-Wide Association Study - statistics and numerical data-
dc.subject.meshModels, Genetic-
dc.subject.meshStatistics, Nonparametric-
dc.titleEvaluating the heritability explained by known susceptibility variants: A survey of ten complex diseasesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0741-0395&volume=35&issue=5&spage=310&epage=317&date=2011&atitle=Evaluating+the+heritability+explained+by+known+susceptibility+variants:+a+survey+of+ten+complex+diseases-
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/gepi.20579en_HK
dc.identifier.pmid21374718-
dc.identifier.scopuseid_2-s2.0-79955841697en_HK
dc.identifier.hkuros188289en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955841697&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume35en_HK
dc.identifier.issue5en_HK
dc.identifier.spage310en_HK
dc.identifier.epage317en_HK
dc.identifier.isiWOS:000291591100003-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectGenome-wide association study of schizophrenia-
dc.identifier.scopusauthoridSo, HC=37031934700en_HK
dc.identifier.scopusauthoridGui, AH=54386819900en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.citeulike9484209-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats