Associations between SNPs in candidate immune-relevant genes and rubella antibody levels

A multigenic assessment

V. Shane Pankratz, Robert A. Vierkant, Megan M. O'Byrne, Inna G. Ovsyannikova, Gregory A. Poland

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses.Results: Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs.Conclusions: For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.

Original languageEnglish (US)
Article number48
JournalBMC Immunology
Volume11
DOIs
StatePublished - Oct 5 2010

Fingerprint

Single Nucleotide Polymorphism
Genes
5' Untranslated Regions
Rubella Vaccine
Measles-Mumps-Rubella Vaccine
rubella antibodies
Interleukin-6
Vaccination

ASJC Scopus subject areas

  • Immunology

Cite this

Pankratz, V. S., Vierkant, R. A., O'Byrne, M. M., Ovsyannikova, I. G., & Poland, G. A. (2010). Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: A multigenic assessment. BMC Immunology, 11, [48]. https://doi.org/10.1186/1471-2172-11-48

Associations between SNPs in candidate immune-relevant genes and rubella antibody levels : A multigenic assessment. / Pankratz, V. Shane; Vierkant, Robert A.; O'Byrne, Megan M.; Ovsyannikova, Inna G.; Poland, Gregory A.

In: BMC Immunology, Vol. 11, 48, 05.10.2010.

Research output: Contribution to journalArticle

Pankratz, V. Shane ; Vierkant, Robert A. ; O'Byrne, Megan M. ; Ovsyannikova, Inna G. ; Poland, Gregory A. / Associations between SNPs in candidate immune-relevant genes and rubella antibody levels : A multigenic assessment. In: BMC Immunology. 2010 ; Vol. 11.
@article{013a895f8a7240de959d1e1966591e14,
title = "Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: A multigenic assessment",
abstract = "Background: The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses.Results: Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs.Conclusions: For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.",
author = "Pankratz, {V. Shane} and Vierkant, {Robert A.} and O'Byrne, {Megan M.} and Ovsyannikova, {Inna G.} and Poland, {Gregory A.}",
year = "2010",
month = "10",
day = "5",
doi = "10.1186/1471-2172-11-48",
language = "English (US)",
volume = "11",
journal = "BMC Immunology",
issn = "1471-2172",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Associations between SNPs in candidate immune-relevant genes and rubella antibody levels

T2 - A multigenic assessment

AU - Pankratz, V. Shane

AU - Vierkant, Robert A.

AU - O'Byrne, Megan M.

AU - Ovsyannikova, Inna G.

AU - Poland, Gregory A.

PY - 2010/10/5

Y1 - 2010/10/5

N2 - Background: The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses.Results: Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs.Conclusions: For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.

AB - Background: The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses.Results: Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs.Conclusions: For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.

UR - http://www.scopus.com/inward/record.url?scp=77957268834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957268834&partnerID=8YFLogxK

U2 - 10.1186/1471-2172-11-48

DO - 10.1186/1471-2172-11-48

M3 - Article

VL - 11

JO - BMC Immunology

JF - BMC Immunology

SN - 1471-2172

M1 - 48

ER -