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Integrative genomic analysis of the human immune response to influenza vaccination.

Franco LM, Bucasas KL, Wells JM, Niño D, Wang X, Zapata GE, Arden N, Renwick A, Yu P, Quarles JM, Bray MS, Couch RB, Belmont JW, Shaw CA - Elife (2013)

Bottom Line: Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy.We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine.More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Human Genetics , Baylor College of Medicine , Houston , United States ; Department of Medicine , Baylor College of Medicine , Houston , United States.

ABSTRACT
Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001.

No MeSH data available.


Study design and integrative analysis scheme.(A) Individuals were immunized on day 0 and peripheral blood RNA samples were obtained on days 0, 1, 3, and 14. Antibody titers were measured on pre-immune sera and on days 14 and 28. Genotyping was carried out on a peripheral blood genomic DNA sample obtained on day 1. Identical sample collection schemes were used, 1 year apart, for the discovery (males) and validation (females) cohorts. (B) Sample sizes and data generation platforms. (C) Integrative analysis involved identification of loci that exhibit a transcriptional response to vaccination, evidence of genetic regulation of expression (constitutive eQTL), evidence of correlation between gene expression and the antibody response, and evidence of correlation between genotype and the antibody response (QTL). Because transcript abundance was measured serially, we were able to evaluate changes in the magnitude of the genetic effect on expression at different time points following vaccination. In addition, the study design permitted QTL analysis conditional on gene expression, which led to the identification of loci whose genetic effects on the antibody response are causally linked through the eQTL.DOI:http://dx.doi.org/10.7554/eLife.00299.010
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fig8: Study design and integrative analysis scheme.(A) Individuals were immunized on day 0 and peripheral blood RNA samples were obtained on days 0, 1, 3, and 14. Antibody titers were measured on pre-immune sera and on days 14 and 28. Genotyping was carried out on a peripheral blood genomic DNA sample obtained on day 1. Identical sample collection schemes were used, 1 year apart, for the discovery (males) and validation (females) cohorts. (B) Sample sizes and data generation platforms. (C) Integrative analysis involved identification of loci that exhibit a transcriptional response to vaccination, evidence of genetic regulation of expression (constitutive eQTL), evidence of correlation between gene expression and the antibody response, and evidence of correlation between genotype and the antibody response (QTL). Because transcript abundance was measured serially, we were able to evaluate changes in the magnitude of the genetic effect on expression at different time points following vaccination. In addition, the study design permitted QTL analysis conditional on gene expression, which led to the identification of loci whose genetic effects on the antibody response are causally linked through the eQTL.DOI:http://dx.doi.org/10.7554/eLife.00299.010

Mentions: A visual representation of the study design, the resulting data sets, and the integrative analysis scheme, is presented in Figure 8.10.7554/eLife.00299.010Figure 8.Study design and integrative analysis scheme.


Integrative genomic analysis of the human immune response to influenza vaccination.

Franco LM, Bucasas KL, Wells JM, Niño D, Wang X, Zapata GE, Arden N, Renwick A, Yu P, Quarles JM, Bray MS, Couch RB, Belmont JW, Shaw CA - Elife (2013)

Study design and integrative analysis scheme.(A) Individuals were immunized on day 0 and peripheral blood RNA samples were obtained on days 0, 1, 3, and 14. Antibody titers were measured on pre-immune sera and on days 14 and 28. Genotyping was carried out on a peripheral blood genomic DNA sample obtained on day 1. Identical sample collection schemes were used, 1 year apart, for the discovery (males) and validation (females) cohorts. (B) Sample sizes and data generation platforms. (C) Integrative analysis involved identification of loci that exhibit a transcriptional response to vaccination, evidence of genetic regulation of expression (constitutive eQTL), evidence of correlation between gene expression and the antibody response, and evidence of correlation between genotype and the antibody response (QTL). Because transcript abundance was measured serially, we were able to evaluate changes in the magnitude of the genetic effect on expression at different time points following vaccination. In addition, the study design permitted QTL analysis conditional on gene expression, which led to the identification of loci whose genetic effects on the antibody response are causally linked through the eQTL.DOI:http://dx.doi.org/10.7554/eLife.00299.010
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3713456&req=5

fig8: Study design and integrative analysis scheme.(A) Individuals were immunized on day 0 and peripheral blood RNA samples were obtained on days 0, 1, 3, and 14. Antibody titers were measured on pre-immune sera and on days 14 and 28. Genotyping was carried out on a peripheral blood genomic DNA sample obtained on day 1. Identical sample collection schemes were used, 1 year apart, for the discovery (males) and validation (females) cohorts. (B) Sample sizes and data generation platforms. (C) Integrative analysis involved identification of loci that exhibit a transcriptional response to vaccination, evidence of genetic regulation of expression (constitutive eQTL), evidence of correlation between gene expression and the antibody response, and evidence of correlation between genotype and the antibody response (QTL). Because transcript abundance was measured serially, we were able to evaluate changes in the magnitude of the genetic effect on expression at different time points following vaccination. In addition, the study design permitted QTL analysis conditional on gene expression, which led to the identification of loci whose genetic effects on the antibody response are causally linked through the eQTL.DOI:http://dx.doi.org/10.7554/eLife.00299.010
Mentions: A visual representation of the study design, the resulting data sets, and the integrative analysis scheme, is presented in Figure 8.10.7554/eLife.00299.010Figure 8.Study design and integrative analysis scheme.

Bottom Line: Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy.We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine.More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Human Genetics , Baylor College of Medicine , Houston , United States ; Department of Medicine , Baylor College of Medicine , Houston , United States.

ABSTRACT
Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001.

No MeSH data available.