Amanda Vinson, PhD - Assistant Professor
Oregon Health & Science University
3181 SW Sam Jackson Park Road
Mail Code # L103A
Portland, OR 97239
Office: 503 418-8391
Fax: 503 494-4411
Heart disease has been described as a disease of low-grade, "smoldering" inflammation, and my research is aimed at understanding how genes and environmental influences contribute to inflammation in coronary heart disease. In particular, I am interested in characterizing genetic effects on T cell-mediated immune response in atherosclerosis. To characterize these effects, I work with both patient populations and non-human primate models of human disease.
With collaborators Drs. Michael Davey and Shannon McWeeney, I am currently conducting a pilot study to assess the contribution of two biomarkers of inflammation to coronary atherosclerosis in patients with rheumatoid arthritis (RA) at the Portland VA Medical Center. Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease characterized by severe joint pathology combined with a 3-fold increased risk of heart attack and >2-fold increased mortality rate from cardiovascular disease (CVD) compared to the general population (del Rincon et al., 2001; Doran et al., 2002; Wolfe et al., 1994). Despite their increased risk of CVD, RA patients do not generally display a corresponding increase in the usual risk factors for CVD (e.g., cholesterol levels). This suggests that the systemic inflammation characteristic of RA is an important risk factor for CVD, independent of traditional risk factors. The goal of this study is to test whether circulating levels of CD4+CD28- T cells and Lp-PLA2 activity (previously implicated in RA pathology and in development of heart disease in the general population) increase our ability to predict coronary atherosclerosis (indicated by coronary artery calcification scores) in RA patients over traditional cardiovascular risk factors alone. In the future, results from this project may be used to support functional genomic and systems genetic studies of implicated cell types.
I also study the genetics of inflammatory and other risk factors for human heart disease in rhesus macaques at the Oregon National Primate Research Center. To do this, I have characterized a single large pedigree of rhesus macaques incorporating over 1,300 animals and spanning 5 generations, for the purposes of quantitative genetic analysis and gene mapping. Using this pedigreed population of rhesus macaques, I have found significant heritability for total cholesterol and multiple hematological traits (N=945), replicating results described in baboons (Mahaney et al., 2005) for these risk factors of human disease. To expand these initial analyses, I am collecting blood samples, as well as morphometric and adiposity measures, on all macaques in this pedigree (~500 animals sampled to date). Extensive phenotyping of these pedigreed animals will permit analyses of heritability, pleiotropic effects, and interaction between genetic and environmental effects (e.g., age, sex, adiposity) for multiple inflammatory, lipid, and other traits associated with human atherosclerosis. I am also interested in developing a SNP-based genetic linkage map in these macaques for the purpose of conducting genome scans and localizing quantitative trait loci (QTLs) that influence risk factors for atherosclerosis and other complex disease.
Vinson A, Curran JE, Johnson MP, Dyer TD, Moses EK, Blangero J, Cox L, Roger J, VandeBerg JL, Havill L, Mahaney MC. Genetical genomics of Th1 and Th2 immune response in a baboon model of atherosclerosis risk factors. (submitted)
Vinson A, Mahaney MC, Diego VP, Cox LA, Rogers J, VandeBerg JL, Rainwater DL. (2008) Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL cholesterol concentration in baboons fed an atherogenic diet. J Lipid Res 49:1295-1302. PMID: 18334716.
Vinson A, Mahaney MC, Cox LA, Rogers J, VandeBerg JL, Rainwater DL. (2008) A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors. Atherosclerosis 196:667-673. PMID:17767937.
Rogers J, Garcia R Jr, Shelledy W, Kaplan J, Arya A, Johnson Z, Bergstrom M, Novakowski L, Nair P, Vinson A, Newman D, Heckman G, Cameron J (2006) An initial genetic linkage map of the rhesus macaque (Macaca mulatta) genome using human microsatellite loci. Genomics 87:30-38. PMID: 16321502
Rogers J, Bergstrom M, Garcia R IV, Kaplan J, Arya A, Novakowski L, Johnson Z, Vinson A, Shelledy W (2005) A panel of 20 highly variable microsatellite polymorphisms in rhesus macaques (Macaca mulatta) selected for pedigree or population genetic analysis. American Journal of Primatology 67:377-383. PMID: 16287107
Westaway SK, Street SL, Searles RP, Vinson A, Ferguson B. (2010) Identification of rhesus macaque SNP variants using a human SNP array. 4th International Primate Genomics Symposium, April 13-15, 2010, Seattle, Washington. (in press)
Vinson A, Diego VP, Goring HHH, Curran JE, Johnson MP, Dyer TD, Moses EK, Rainwater DL, Comuzzie AG, MacCluer JW, Blangero J, Mahaney MC. (2009) Pleiotropic effects on T cell activation are associated with PDAY (Pathobiological Determinants of Atherosclerosis in Youth) risk score in the San Antonio Family Heart Study. (Program #56) Podium presentation at the 59th Annual Meeting of The American Society of Human Genetics, October 22, 2009, Honolulu, HI.
Diego VP, Vinson A, Higgins PB, Peralta JM, Charlesworth J, Cole SA, Dyer, TD, Curran JE, Johnson MP, Moses EK, Goring HHH, Almasy L, Comuzzie AG, Rainwater DL, Mahaney MC, MacCluer JW, Blangero J, Williams-Blangero S. (2009) Genetical genomic analyses of the nuclear factor-κ B signal transduction network: detection of emergent system-level properties relevant to the aging process. (Program #913/W) Poster presentation at the 59th Annual Meeting of The American Society of Human Genetics, October 21, 2009, Honolulu, HI.
Havill LM, Vinson A, Blangero J, Curran JE, Johnson MP, Platt OS, Brugnara C, Mahaney MC. Gene transcripts related to T-cell activation, proliferation, and cytokine signaling show significant effects on BMD variation in baboons. (2008) Poster presentation at the 30th annual meeting of the American Society for Bone & Mineral Research, J. Bone Miner Res. 2008 Sep;23(Suppl 1):S433.
Vinson A, Goring HH, Curran JE, Johnson MP, Dyer TD, Newman DE, Cole SA, Cox LA, Rogers J, VandeBerg JL, Brugnara C, Platt OS, Moses EK, Blangero J, Mahaney MC. (2008) Replication between humans and baboons of quantitative trait loci that regulate the expression of genes implicated in T-cell mediated effects on atherosclerosis. Podium presentation, 3rd International Conference on Primate Genomics, “Primate Genomics and Human Disease”, Seattle, WA.
Vinson A, Curran JE, Johnson MP, Dyer TD, Moses EK, Blangero J, Cole SA, Cox LA, Roger J, VandeBerg JL, Brugnara C, Platt, OS, Mahaney MC. (2007) Genetic effects on the expression of genes implicated in human T-cell regulation of inflammation in pedigreed baboons. Poster presentation, The American Society of Human Genetics annual meeting, October, San Diego, CA. The American Society of Human Genetics Abstracts, 57th Annual Meeting:232
Vinson A, Bottini N, Newman DE, Dyer TD, Jett CM, Johnson MP, Curran JE, Moses EK, Blangero J, Cole SA, Cox LA, Rogers J, VandeBerg JL, Brugnara C, Platt OS, Mahaney MC. Genetic contributions to normal variation in expression of a gene associated with susceptibility to multiple human autoimmune disorders (PTPN22) in baboons. (2007) Poster presentation, American Association of Physical Anthropologists annual meeting, Philadelphia, PA. American Journal of Physical Anthropology 132 (S44):239
Vinson A, Mahaney MC, Cox LA, Rogers J, VandeBerg JL, Rainwater DL. Diet-specific quantitative trait loci affecting variation in serum platelet-activating factor acetylhydrolase activity in baboons fed basal and atherogenic diets. (2006) Moderated poster presentation #1035, American Heart Association Scientific Sessions annual meeting, November, Chicago, IL. Circulation S114(18):II-190
Vinson A, Mahaney MC, Cox LA, Rogers J, VandeBerg JL, Rainwater DL. A QTL influencing both serum PAF-AH activity and LDL cholesterol concentration maps to the baboon ortholog of human chromosome 2p. (2006) Poster presentation, The American Society of Human Genetics annual meeting, October, New Orleans, LA. The American Society of Human Genetics Abstracts, 56th Annual Meeting:110
Vinson A, Rainwater DL, Cox LA, Rogers J,VandeBerg JL, and Mahaney MC. Two QTLs affecting normal variation of plasma PAF-AH in baboons map to the baboon orthologs of human chromosomes 2p and 16. (2006) Podium presentation, American Society of Primatologists annual meeting, August, San Antonio, TX. American Journal of Primatology S68(1):135
Vinson A, Packer C, Rogers J. Genetic differentiation among social groups of savannah baboons at Gombe National Park and Mikumi National Park, Tanzania: Significance and relative contribution by age-class and sex. (2006) Podium presentation, American Association of Physical Anthropologists annual meeting, American Journal of Physical Anthropology S4:182
Vinson A, Packer C, Rogers J. Patterns of relatedness and the population genetic effects of male-biased dispersal in savannah baboons at Gombe National Park and Mikumi National Park, Tanzania. (2005) Podium presentation, American Association of Physical Anthropologists annual meeting. American Journal of Physical Anthropology S40:214
Vinson A, Packer C, Rogers J. An optimized panel of microsatellites for fecal DNA studies of wild baboons: preliminary analyses of genetic variation among Gombe baboons. (2003) Poster presentation, American Association of Physical Anthropologists annual meeting. American Journal of Physical Anthropology S36:215-216
Vinson A, Packer C, Rogers J. Genetic analyses of Gombe baboons from fecal DNA: Methods and preliminary results describing genetic variation at 16 microsatellites. (2003) Poster presentation, Texas Genetics Society annual meeting. Proceedings of the 30th Annual Meeting of the Texas Genetics Society:
Amanda Vinson is an Assistant Professor in the Dept. of Molecular and Medical Genetics, an Assistant Scientist in the Division of Neuroscience at the Oregon National Primate Research Center, and has a joint appointment in the Division of Bioinformatics and Computational Biology in the Dept. of Medical Informatics & Clinical Epidemiology at OHSU. She received her Ph.D. in population genetics from the Dept. of Ecology, Evolution & Behavior at the University of Minnesota, Twin Cities. During her postdoctoral fellowship at the Southwest Foundation for Biomedical Research/Southwest National Primate Research Center, she used a variance components approach to characterize heritability, pleiotropy, and QTL effects on Lp-PLA2 activity and LDL cholesterol levels in pedigreed baboons, and on gene expression implicated in T-helper cell immune response in both pedigreed baboons, and in the San Antonio Family Heart Study. In addition to conducting research, Dr. Vinson is also the director of the Colony Genetics & Demographics unit within the Primate Genetics Program at the ONPRC. In this capacity, she is responsible for pedigree characterization of all ONPRC primate colonies, and for providing support to colony management personnel on issues that impact the genetic health and diversity of all non-human primates at the ONPRC.