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dc.contributor.authorBachmann, Nadine
dc.contributor.authorTurk, Teja
dc.contributor.authorKadelka, Claus
dc.contributor.authorMarzel, Alex
dc.contributor.authorShilaih, Mohaned
dc.contributor.authorBöni, Jürg
dc.contributor.authorAubert, Vincent
dc.contributor.authorKlimkait, Thomas
dc.contributor.authorLeventhal, Gabriel E
dc.contributor.authorGünthard, Huldrych F
dc.contributor.authorKouyos, Roger
dc.contributor.authorGünthard, Huldrych F.
dc.contributor.authorSwiss HIV Cohort Study
dc.contributor.authorLeventhal, Gabriel Etan
dc.date.accessioned2017-05-30T15:35:29Z
dc.date.available2017-05-30T15:35:29Z
dc.date.issued2017-05
dc.date.submitted2017-03
dc.identifier.issn1742-4690
dc.identifier.urihttp://hdl.handle.net/1721.1/109413
dc.description.abstractBackground Parent-offspring (PO) regression is a central tool to determine the heritability of phenotypic traits; i.e., the relative extent to which those traits are controlled by genetic factors. The applicability of PO regression to viral traits is unclear because the direction of viral transmission—who is the donor (parent) and who is the recipient (offspring)—is typically unknown and viral phylogenies are sparsely sampled. Methods We assessed the applicability of PO regression in a realistic setting using Ornstein–Uhlenbeck simulated data on phylogenies built from 11,442 Swiss HIV Cohort Study (SHCS) partial pol sequences and set-point viral load (SPVL) data from 3293 patients. Results We found that the misidentification of donor and recipient plays a minor role in estimating heritability and showed that sparse sampling does not influence the mean heritability estimated by PO regression. A mixed-effect model approach yielded the same heritability as PO regression but could be extended to clusters of size greater than 2 and allowed for the correction of confounding effects. Finally, we used both methods to estimate SPVL heritability in the SHCS. We employed a wide range of transmission pair criteria to measure heritability and found a strong dependence of the heritability estimates to these criteria. For the most conservative genetic distance criteria, for which heritability estimates are conceptually expected to be closest to true heritability, we found estimates ranging from 32 to 46% across different bootstrap criteria. For less conservative distance criteria, we found estimates ranging down to 8%. All estimates did not change substantially after adjusting for host-demographic factors in the mixed-effect model (±2%). Conclusions For conservative transmission pair criteria, both PO regression and mixed-effect models are flexible and robust tools to estimate the contribution of viral genetic effects to viral traits under real-world settings. Overall, we find a strong effect of viral genetics on SPVL that is not confounded by host demographics.en_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofhttp://dx.doi.org/10.1186/s12977-017-0356-3en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceBioMed Centralen_US
dc.titleParent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setupen_US
dc.typeArticleen_US
dc.identifier.citationBachmann, Nadine; Turk, Teja; Kadelka, Claus; Marzel, Alex; Shilaih, Mohaned; Böni, Jürg; Aubert, Vincent et al. "Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup." BioMed Central 14, no. 33: 1-10 © 2017 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Civil and Environmental Engineeringen_US
dc.contributor.mitauthorLeventhal, Gabriel Etan
dc.relation.journalRetrovirologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2017-05-28T03:26:22Z
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dspace.orderedauthorsBachmann, Nadine; Turk, Teja; Kadelka, Claus; Marzel, Alex; Shilaih, Mohaned; Böni, Jürg; Aubert, Vincent; Klimkait, Thomas; Leventhal, Gabriel E.; Günthard, Huldrych F.; Kouyos, Rogeren_US
dspace.embargo.termsNen_US
mit.licensePUBLISHER_CCen_US


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