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dc.contributor.author
Bachmann, Nadine
dc.contributor.author
Turk, Teja
dc.contributor.author
Kadelka, Claus
dc.contributor.author
Marzel, Alex
dc.contributor.author
Shilaih, Mohaned
dc.contributor.author
Böni, Jürg
dc.contributor.author
Aubert, Vincent
dc.contributor.author
Klimkait, Thomas
dc.contributor.author
Leventhal, Gabriel E.
dc.contributor.author
Günthard, Huldrych F.
dc.contributor.author
Kouyos, Roger
dc.contributor.author
Swiss HIV Cohort Study
dc.date.accessioned
2017-11-20T16:40:55Z
dc.date.available
2017-10-06T03:27:48Z
dc.date.available
2017-11-20T16:40:55Z
dc.date.issued
2017
dc.identifier.issn
1742-4690
dc.identifier.other
10.1186/s12977-017-0356-3
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/191634
dc.identifier.doi
10.3929/ethz-b-000191634
dc.description.abstract
Background 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.language.iso
en
en_US
dc.publisher
Biomed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
HIV-1
en_US
dc.subject
Set-point viral load
en_US
dc.subject
Parent-offspring regression
en_US
dc.subject
Ornstein-Uhlenbeck process
en_US
dc.subject
Heritability
en_US
dc.subject
Mixed-effect model
en_US
dc.title
Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-05-23
ethz.journal.title
Retrovirology
ethz.journal.volume
14
en_US
ethz.journal.abbreviated
Retrovirology
ethz.pages.start
33
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-10-06T03:27:57Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-11-20T16:41:03Z
ethz.rosetta.lastUpdated
2017-11-20T16:41:03Z
ethz.rosetta.versionExported
true
ethz.COinS
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