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Using information of relatives in genomic prediction to apply effective stratified medicine

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dc.contributor.authorLee, S.H.
dc.contributor.authorWeerasinghe, W.M.S.P.
dc.contributor.authorWray, N.R.
dc.contributor.authorGoddard, M.E.
dc.contributor.authorvan der Werf, J.H.J.
dc.date.issued2017
dc.description.abstractGenomic prediction shows promise for personalised medicine in which diagnosis and treatment are tailored to individuals based on their genetic profiles for complex diseases. We present a theoretical framework to demonstrate that prediction accuracy can be improved by targeting more informative individuals in the data set used to generate the predictors ("discovery sample") to include those with genetically close relationships with the subjects put forward for risk prediction. Increase of prediction accuracy from closer relationships is achieved under an additive model and does not rely on any family or interaction effects. Using theory, simulations and real data analyses, we show that the predictive accuracy or the area under the receiver operating characteristic curve (AUC) increased exponentially with decreasing effective size (N-e), i. e. when individuals are closely related. For example, with the sample size of discovery set N = 3000, heritability h(2) = 0.5 and population prevalence K = 0.1, AUC value approached to 0.9 and the top percentile of the estimated genetic profile scores had 23 times higher proportion of cases than the general population. This suggests that there is considerable room to increase prediction accuracy by using a design that does not exclude closer relationships.
dc.identifier.citationScientific Reports, 2017; 7(article no. 42091):1-13
dc.identifier.doi10.1038/srep42091
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidLee, S.H. [0000-0001-9701-2718]
dc.identifier.urihttps://hdl.handle.net/11541.2/130832
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.fundingNHMRC 1080157
dc.relation.fundingNHMRC 1087889
dc.relation.fundingNHMRC 1078901
dc.relation.fundingARC DP160102126
dc.relation.fundingARC FT160100229
dc.rightsCopyright 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/)
dc.source.urihttp://dx.doi.org/10.1038/srep42091
dc.subjectgenomic prediction
dc.subjectpersonalised medicine
dc.subjectmissing heritability
dc.titleUsing information of relatives in genomic prediction to apply effective stratified medicine
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916175886301831

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