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dc.contributor.authorChen, Fangen_US
dc.contributor.authorHe, Jingen_US
dc.contributor.authorZhang, Jianqien_US
dc.contributor.authorChen, Gary K.en_US
dc.contributor.authorThomas, Venettaen_US
dc.contributor.authorAmbrosone, Christine B.en_US
dc.contributor.authorBandera, Elisa V.en_US
dc.contributor.authorBerndt, Sonja I.en_US
dc.contributor.authorBernstein, Leslieen_US
dc.contributor.authorBlot, William J.en_US
dc.contributor.authorCai, Qiuyinen_US
dc.contributor.authorCarpten, Johnen_US
dc.contributor.authorCasey, Grahamen_US
dc.contributor.authorChanock, Stephen J.en_US
dc.contributor.authorCheng, Ionaen_US
dc.contributor.authorChu, Lisaen_US
dc.contributor.authorDeming, Sandra L.en_US
dc.contributor.authorDriver, W. Ryanen_US
dc.contributor.authorGoodman, Phyllisen_US
dc.contributor.authorHayes, Richard B.en_US
dc.contributor.authorHennis, Anselm J. M.en_US
dc.contributor.authorHsing, Ann W.en_US
dc.contributor.authorHu, Jennifer J.en_US
dc.contributor.authorIngles, Sue A.en_US
dc.contributor.authorJohn, Esther M.en_US
dc.contributor.authorKittles, Rick A.en_US
dc.contributor.authorKolb, Suzanneen_US
dc.contributor.authorLeske, M. Cristinaen_US
dc.contributor.authorMillikan, Robert C.en_US
dc.contributor.authorMonroe, Kristine R.en_US
dc.contributor.authorMurphy, Adamen_US
dc.contributor.authorNemesure, Barbaraen_US
dc.contributor.authorNeslund-Dudas, Christineen_US
dc.contributor.authorNyante, Sarahen_US
dc.contributor.authorOstrander, Elaine Aen_US
dc.contributor.authorPress, Michael F.en_US
dc.contributor.authorRodriguez-Gil, Jorge L.en_US
dc.contributor.authorRybicki, Ben A.en_US
dc.contributor.authorSchumacher, Fredricken_US
dc.contributor.authorStanford, Janet L.en_US
dc.contributor.authorSignorello, Lisa B.en_US
dc.contributor.authorStrom, Sara S.en_US
dc.contributor.authorStevens, Victoriaen_US
dc.contributor.authorVan Den Berg, Daviden_US
dc.contributor.authorWang, Zhaomingen_US
dc.contributor.authorWitte, John S.en_US
dc.contributor.authorWu, Suh-Yuhen_US
dc.contributor.authorYamamura, Yukoen_US
dc.contributor.authorZheng, Weien_US
dc.contributor.authorZiegler, Regina G.en_US
dc.contributor.authorStram, Alexander H.en_US
dc.contributor.authorKolonel, Laurence N.en_US
dc.contributor.authorMarchand, Loïc Leen_US
dc.contributor.authorHenderson, Brian E.en_US
dc.contributor.authorHaiman, Christopher A.en_US
dc.contributor.authorStram, Daniel O.en_US
dc.date.accessioned2015-08-03T14:00:02Z
dc.date.issued2015en_US
dc.identifier.citationChen, F., J. He, J. Zhang, G. K. Chen, V. Thomas, C. B. Ambrosone, E. V. Bandera, et al. 2015. “Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.” PLoS ONE 10 (6): e0131106. doi:10.1371/journal.pone.0131106. http://dx.doi.org/10.1371/journal.pone.0131106.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17820721
dc.description.abstractHeight has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0131106en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488332/pdf/en
dash.licenseLAAen_US
dc.titleMethodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adultsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorSignorello, Lisa B.en_US
dc.date.available2015-08-03T14:00:02Z
dc.identifier.doi10.1371/journal.pone.0131106*
dash.authorsorderedfalse
dash.contributor.affiliatedSignorello, Lisa B


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