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Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment.

Pankratz VS, Vierkant RA, O'Byrne MM, Ovsyannikova IG, Poland GA - BMC Immunol. (2010)

Bottom Line: The mechanisms of immune response are structured within a highly complex regulatory system.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.It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. pankratz.vernon@mayo.edu

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.

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Related in: MedlinePlus

Quantile plot of observed versus expected p-values (on the logarithmic scale) for the associations between the combinations formed from each possible pair of SNPs and rubella antibody levels. While the observed p-values depart somewhat from the line of unity, they do not follow a pattern that suggests the presence of major epistatic effects.
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Figure 2: Quantile plot of observed versus expected p-values (on the logarithmic scale) for the associations between the combinations formed from each possible pair of SNPs and rubella antibody levels. While the observed p-values depart somewhat from the line of unity, they do not follow a pattern that suggests the presence of major epistatic effects.

Mentions: The plot in Figure 2 represents the results from the analysis of the associations between the 263,175 possible pair-wise combinations of SNPs and rubella antibody levels. The observed p-values deviate somewhat from the line of unity, but not in a way that is indicative of the presence of a small number of pairs of SNPs that are strongly associated with rubella antibody levels. In fact, the smallest p-value of 1.07 × 10-5 for the combination of rs10489626, an intronic SNP in IL12RB2, and rs1420094, a 3' flanking SNP in IL18R1, was actually less extreme than what would be expected if there were no pair-wise epistatic associations present.


Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment.

Pankratz VS, Vierkant RA, O'Byrne MM, Ovsyannikova IG, Poland GA - BMC Immunol. (2010)

Quantile plot of observed versus expected p-values (on the logarithmic scale) for the associations between the combinations formed from each possible pair of SNPs and rubella antibody levels. While the observed p-values depart somewhat from the line of unity, they do not follow a pattern that suggests the presence of major epistatic effects.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965704&req=5

Figure 2: Quantile plot of observed versus expected p-values (on the logarithmic scale) for the associations between the combinations formed from each possible pair of SNPs and rubella antibody levels. While the observed p-values depart somewhat from the line of unity, they do not follow a pattern that suggests the presence of major epistatic effects.
Mentions: The plot in Figure 2 represents the results from the analysis of the associations between the 263,175 possible pair-wise combinations of SNPs and rubella antibody levels. The observed p-values deviate somewhat from the line of unity, but not in a way that is indicative of the presence of a small number of pairs of SNPs that are strongly associated with rubella antibody levels. In fact, the smallest p-value of 1.07 × 10-5 for the combination of rs10489626, an intronic SNP in IL12RB2, and rs1420094, a 3' flanking SNP in IL18R1, was actually less extreme than what would be expected if there were no pair-wise epistatic associations present.

Bottom Line: The mechanisms of immune response are structured within a highly complex regulatory system.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.It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. pankratz.vernon@mayo.edu

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.

Show MeSH
Related in: MedlinePlus