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How effectively can HIV phylogenies be used to measure heritability?


Shirreff, George; Alizon, Samuel; Cori, Anne; Gunthard, Huldrych F; Laeyendecker, Oliver; van Sighem, Ard; Bezemer, Daniela; Fraser, Christophe (2013). How effectively can HIV phylogenies be used to measure heritability? Evolution, Medicine, and Public Health, 2013(1):209-224.

Abstract

Background and objectives: The severity of HIV-1 infection, measured by set-point viral load (SPVL), is highly variable between individuals. Its heritability between infections quantifies the control the pathogen genotype has over disease severity. Heritability estimates vary widely between studies, but differences in methods make comparison difficult. Phylogenetic comparative analysis offers measures of phylogenetic signal, but it is unclear how to interpret them in terms of the fraction of variance in SPVL controlled by the virus genotype.
Methodology: We present computational methods which link statistics summarizing phylogenetic signal to heritability, h2 in order to test for and quantify it. We re-analyse data from Switzerland and Uganda, and apply it to new data from the Netherlands. We systematically compare established and new (e.g. phylogenetic pairs, PP) phylogenetic signal statistics.
Results: Heritability estimates varied by method and dataset. Several methods were consistently able to detect simulated heritability above Graphic, but none below. Pagel’s λ was the most robust and sensitive. The PP method found no heritability in the Netherlands data, whereas Pagel’s λ found significant heritability only in a narrow subdivision (P = 0.038). Heritability was estimated at h2 = 0.52 (95% confidence interval 0.00–0.63).
Conclusions and implications: This standardized measure, h2, allows comparability of heritability between cohorts. We confirm high heritability in Swiss data, but neither in Ugandan data nor in the Netherlands, where it is barely significant or undetectable. Existing phylogenetic methods are ill-suited for detecting heritability below Graphic, which may nonetheless be biologically important.

Abstract

Background and objectives: The severity of HIV-1 infection, measured by set-point viral load (SPVL), is highly variable between individuals. Its heritability between infections quantifies the control the pathogen genotype has over disease severity. Heritability estimates vary widely between studies, but differences in methods make comparison difficult. Phylogenetic comparative analysis offers measures of phylogenetic signal, but it is unclear how to interpret them in terms of the fraction of variance in SPVL controlled by the virus genotype.
Methodology: We present computational methods which link statistics summarizing phylogenetic signal to heritability, h2 in order to test for and quantify it. We re-analyse data from Switzerland and Uganda, and apply it to new data from the Netherlands. We systematically compare established and new (e.g. phylogenetic pairs, PP) phylogenetic signal statistics.
Results: Heritability estimates varied by method and dataset. Several methods were consistently able to detect simulated heritability above Graphic, but none below. Pagel’s λ was the most robust and sensitive. The PP method found no heritability in the Netherlands data, whereas Pagel’s λ found significant heritability only in a narrow subdivision (P = 0.038). Heritability was estimated at h2 = 0.52 (95% confidence interval 0.00–0.63).
Conclusions and implications: This standardized measure, h2, allows comparability of heritability between cohorts. We confirm high heritability in Swiss data, but neither in Ugandan data nor in the Netherlands, where it is barely significant or undetectable. Existing phylogenetic methods are ill-suited for detecting heritability below Graphic, which may nonetheless be biologically important.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:08 Jan 2014 08:31
Last Modified:05 Apr 2016 17:20
Publisher:Oxford University Press
ISSN:2050-6201
Additional Information:This article has been accepted for publication in Evolution, Medicine, and Public Health Published by Oxford University Press
Publisher DOI:https://doi.org/10.1093/emph/eot019

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