Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup
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 t...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12977-017-0356-3 |
| _version_ | 1829099737361416192 |
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| author | Nadine Bachmann Teja Turk Claus Kadelka Alex Marzel Mohaned Shilaih Jürg Böni Vincent Aubert Thomas Klimkait Gabriel E. Leventhal Huldrych F. Günthard Roger Kouyos the Swiss HIV Cohort Study |
| author_facet | Nadine Bachmann Teja Turk Claus Kadelka Alex Marzel Mohaned Shilaih Jürg Böni Vincent Aubert Thomas Klimkait Gabriel E. Leventhal Huldrych F. Günthard Roger Kouyos the Swiss HIV Cohort Study |
| author_sort | Nadine Bachmann |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T22:23:56Z |
| format | Article |
| id | doaj.art-3a5a6e71eb4c4ed9865ffa9df9c60058 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-10T22:23:56Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-3a5a6e71eb4c4ed9865ffa9df9c600582022-12-22T01:31:14ZengBMCRetrovirology1742-46902017-05-0114111010.1186/s12977-017-0356-3Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setupNadine Bachmann0Teja Turk1Claus Kadelka2Alex Marzel3Mohaned Shilaih4Jürg Böni5Vincent Aubert6Thomas Klimkait7Gabriel E. Leventhal8Huldrych F. Günthard9Roger Kouyos10the Swiss HIV Cohort StudyDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichInstitute of Medical Virology, University of ZurichDivisions of Immunology and Allergy, University Hospital LausanneMolecular Virology, Department Biomedicine - Petersplatz, University of BaselDepartment of Environmental Systems Science, ETH ZurichDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital ZurichAbstract 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.http://link.springer.com/article/10.1186/s12977-017-0356-3HeritabilityParent-offspring regressionHIV-1Set-point viral loadOrnstein–Uhlenbeck processMixed-effect model |
| spellingShingle | Nadine Bachmann Teja Turk Claus Kadelka Alex Marzel Mohaned Shilaih Jürg Böni Vincent Aubert Thomas Klimkait Gabriel E. Leventhal Huldrych F. Günthard Roger Kouyos the Swiss HIV Cohort Study Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup Retrovirology Heritability Parent-offspring regression HIV-1 Set-point viral load Ornstein–Uhlenbeck process Mixed-effect model |
| title | Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup |
| title_full | Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup |
| title_fullStr | Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup |
| title_full_unstemmed | Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup |
| title_short | Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup |
| title_sort | parent offspring regression to estimate the heritability of an hiv 1 trait in a realistic setup |
| topic | Heritability Parent-offspring regression HIV-1 Set-point viral load Ornstein–Uhlenbeck process Mixed-effect model |
| url | http://link.springer.com/article/10.1186/s12977-017-0356-3 |
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