Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central
2017
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| Online Access: | http://hdl.handle.net/1721.1/109413 |
| _version_ | 1811087518077026304 |
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| author | Bachmann, Nadine Turk, Teja Kadelka, Claus Marzel, Alex Shilaih, Mohaned Böni, Jürg Aubert, Vincent Klimkait, Thomas Leventhal, Gabriel E Günthard, Huldrych F Kouyos, Roger Günthard, Huldrych F. Swiss HIV Cohort Study Leventhal, Gabriel Etan |
| author2 | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Bachmann, Nadine Turk, Teja Kadelka, Claus Marzel, Alex Shilaih, Mohaned Böni, Jürg Aubert, Vincent Klimkait, Thomas Leventhal, Gabriel E Günthard, Huldrych F Kouyos, Roger Günthard, Huldrych F. Swiss HIV Cohort Study Leventhal, Gabriel Etan |
| author_sort | Bachmann, Nadine |
| collection | MIT |
| description | 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 | 2024-09-23T13:47:22Z |
| format | Article |
| id | mit-1721.1/109413 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:47:22Z |
| publishDate | 2017 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1094132022-09-28T16:12:40Z Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup Bachmann, Nadine Turk, Teja Kadelka, Claus Marzel, Alex Shilaih, Mohaned Böni, Jürg Aubert, Vincent Klimkait, Thomas Leventhal, Gabriel E Günthard, Huldrych F Kouyos, Roger Günthard, Huldrych F. Swiss HIV Cohort Study Leventhal, Gabriel Etan Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Leventhal, Gabriel Etan 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. 2017-05-30T15:35:29Z 2017-05-30T15:35:29Z 2017-05 2017-03 2017-05-28T03:26:22Z Article http://purl.org/eprint/type/JournalArticle 1742-4690 http://hdl.handle.net/1721.1/109413 Bachmann, 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 http://dx.doi.org/10.1186/s12977-017-0356-3 Retrovirology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Bachmann, Nadine Turk, Teja Kadelka, Claus Marzel, Alex Shilaih, Mohaned Böni, Jürg Aubert, Vincent Klimkait, Thomas Leventhal, Gabriel E Günthard, Huldrych F Kouyos, Roger Günthard, Huldrych F. Swiss HIV Cohort Study Leventhal, Gabriel Etan Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup |
| 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 |
| url | http://hdl.handle.net/1721.1/109413 |
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