Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors

Amanda Vinson, J. E. Curran, M. P. Johnson, T. D. Dyer, E. K. Moses, J. Blangero, L. A. Cox, J. Rogers, L. M. Havill, J. L. VandeBerg, M. C. Mahaney

    Research output: Contribution to journalArticle

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    Abstract

    CD4 + T-cells mediate inflammation in atherosclerosis, but additive genetic effects on associated pathways of Th1 and Th2 immune response have not been described. We sought to characterize heritability, pleiotropy, and QTL effects on the expression of genes implicated in Th1 and Th2 immune response in a baboon model of risk factors for atherosclerosis. Methods: We employed a maximum likelihood-based variance decomposition approach to estimate additive genetic effects on transcript levels generated from a gene expression profile of lymphocytes in 499 pedigreed baboons maintained on a basal diet. Transcript levels for 57 genes implicated in Th1 and Th2 immune response were selected for analysis based on significant heritability in this profile. Multipoint whole genome scans were conducted on heritable transcript levels to localize QTLs influencing these measures. To evaluate pleiotropic effects on transcript levels, we estimated genetic and phenotypic correlations among transcript measures, and assessed their correspondence using a Mantel test. Network analysis using GeneGo's MetaCore™ software was conducted to characterize known interaction among coded proteins. Results: Heritabilities for candidate gene transcript levels ranged from 0.092-0.786 (median h 2=0.278, P=4.72×10 -4). Linkage analyses yielded significant evidence (LOD≥2.73) for 14 eQTLs (LOD score range 2.76-14.87, genome-wide P=4.9×10 -2-1.03×10 -14). Estimates of genetic correlation supported shared additive genetic effects incorporating all 57 transcripts (null hypothesis of ρ G=0 rejected at FDR≤0.05 for 522 of 1596 estimates), and accounted for most of the observed phenotypic correlation among transcripts (Mantel test, r [ρ P], [ρ G]=0.781, P

    Original languageEnglish (US)
    Pages (from-to)387-394
    Number of pages8
    JournalAtherosclerosis
    Volume217
    Issue number2
    DOIs
    StatePublished - Aug 2011

    Fingerprint

    Papio
    Genomics
    Atherosclerosis
    Genome
    Transcriptome
    Genes
    Software
    Lymphocytes
    Diet
    Inflammation
    T-Lymphocytes
    Gene Expression
    Proteins

    Keywords

    • Atherosclerosis
    • Baboon
    • Gene expression
    • Inflammation
    • QTL
    • Th1
    • Th2

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Vinson, A., Curran, J. E., Johnson, M. P., Dyer, T. D., Moses, E. K., Blangero, J., ... Mahaney, M. C. (2011). Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors. Atherosclerosis, 217(2), 387-394. https://doi.org/10.1016/j.atherosclerosis.2011.06.015

    Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors. / Vinson, Amanda; Curran, J. E.; Johnson, M. P.; Dyer, T. D.; Moses, E. K.; Blangero, J.; Cox, L. A.; Rogers, J.; Havill, L. M.; VandeBerg, J. L.; Mahaney, M. C.

    In: Atherosclerosis, Vol. 217, No. 2, 08.2011, p. 387-394.

    Research output: Contribution to journalArticle

    Vinson, A, Curran, JE, Johnson, MP, Dyer, TD, Moses, EK, Blangero, J, Cox, LA, Rogers, J, Havill, LM, VandeBerg, JL & Mahaney, MC 2011, 'Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors', Atherosclerosis, vol. 217, no. 2, pp. 387-394. https://doi.org/10.1016/j.atherosclerosis.2011.06.015
    Vinson, Amanda ; Curran, J. E. ; Johnson, M. P. ; Dyer, T. D. ; Moses, E. K. ; Blangero, J. ; Cox, L. A. ; Rogers, J. ; Havill, L. M. ; VandeBerg, J. L. ; Mahaney, M. C. / Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors. In: Atherosclerosis. 2011 ; Vol. 217, No. 2. pp. 387-394.
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    AU - Dyer, T. D.

    AU - Moses, E. K.

    AU - Blangero, J.

    AU - Cox, L. A.

    AU - Rogers, J.

    AU - Havill, L. M.

    AU - VandeBerg, J. L.

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    KW - Th2

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