Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

Toxicology and Applied Pharmacology

Volumn 271, Issue 3, 2013, Pages 395-404

  Mortensen, Holly M ^a   Euling, Susan Y ^a  

^a U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Bioinformatics; Human genetic variation; Susceptibility; Toxicity pathway

Indexed keywords

ENVIRONMENTAL CHEMICAL;

ARTICLE; ENVIRONMENTAL IMPACT ASSESSMENT; GENE LOCUS; GENETIC HETEROGENEITY; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOMICS; GENOTYPE; HEALTH HAZARD; HIGH THROUGHPUT SEQUENCING; HUMAN; METABOLOMICS; PROTEOMICS; SINGLE NUCLEOTIDE POLYMORPHISM; SUSCEPTIBLE POPULATION; TRANSCRIPTOMICS;

-OMICS; ACTOR; AGGREGATED COMPUTATIONAL TOXICOLOGY RESOURCES; BIOINFORMATICS; CNV; COPY NUMBER VARIANT; DBSNP; DIABETES TYPE 2; EGP; ENVIRONMENT-WIDE ASSOCIATION STUDY; EPA'S CHEMICAL PRIORITIZATION RESEARCH PROGRAM; EWAS; GENOME-WIDE ASSOCIATION STUDY; GWAS; HAPMAP; HIGH-THROUGHPUT SCREENING; HIGH-THROUGHPUT/HIGH CONTENT; HT/HC; HTS; HUMAN GENETIC VARIATION; INTEGRATED RISK INFORMATION SYSTEM; INTERNATIONAL HAPLOTYPE MAP (HAPMAP) PROJECT; IRIS; MOA; MODE OF ACTION; NAS; NATIONAL ACADEMY OF SCIENCES; NATIONAL CENTER FOR BIOTECHNOLOGY; NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; NCBI; NEOLOGISM RELATING MULTIPLE FIELDS IN BIOLOGY THAT END IN -OMICS (E.G., GENOMICS, TRANSCIPTOMICS, PROTEOMICS, METABOLOMICS); NIEHS; NIEHS-ENVIRONMENTAL GENOME PROJECT; NR; NUCLEAR RECEPTOR; PDR; POLYMORPHISM DISCOVERY RESOURCE; REFERENCE CONCENTRATION; REFERENCE DOSE; RFC; RFD; SINGLE NUCLEOTIDE POLYMORPHISM; SINGLE NUCLEOTIDE POLYMORPHISM DATABASE; SNP; SUSCEPTIBILITY; TD; TD2; TK; TOXCAST; TOXICITY PATHWAY; TOXICODYNAMICS; TOXICOKINETICS; TRANSCRIPTION START SITE; TSS; UF; UNCERTAINTY/VARIABILITY FACTOR; US ENVIRONMENTAL PROTECTION AGENCY; US EPA;

DATABASES, FACTUAL; ENVIRONMENTAL POLLUTANTS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; POLYMORPHISM, GENETIC; RISK ASSESSMENT;

EID: 84883741004     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2011.01.015     Document Type: Article

References (91)

1. Andersen M.E., Clewell H.J., Bermudez E., Dodd D.E., Willson G.A., Campbell J.L., Thomas R.S. Formaldehyde: integrating dosimetry, cytotoxicity, and genomics to understand dose-dependent transitions for an endogenous compound. Toxicol. Sci. 2010, 118:716-731.
2. Arnaud C.H. Exposing the exposome. Chemical and Engineering News 2010, 42-44.
3. Boguski M.S. Comparative genomics: the mouse that roared. Nature 2002, 420:515-516.
4. Butcher E.C., Berg E.L., Kunkel E.J. Systems biology in drug discovery. Nat. Biotechnol. 2004, 22:1253-1259.
5. Campbell M.C., Tishkoff S.A. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu. Rev. Genomics Hum. Genet. 2008, 9:403-433.
6. Chen J., Aronow B.J., Jegga A.G. Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinform. 2009, 10:73.
7. Cheung V.G., Spielman R.S., Ewens K.G., Weber T.M., Morley M., Burdick J.T. Mapping determinants of human gene expression by regional and genome-wide association. Nature 2005, 437:1365-1369.
8. Clark A.G., Hubisz M.J., Bustamante C.D., Williamson S.H., Nielsen R. Ascertainment bias in studies of human genome-wide polymorphism. Genome Res. 2005, 15:1496-1502.
9. Clayton D.G., Walker N.M., Smyth D.J., Pask R., Cooper J.D., Maier L.M., Smink L.J., Lam A.C., Ovington N.R., Stevens H.E., Nutland S., Howson J.M., Faham M., Moorhead M., Jones H.B., Falkowski M., Hardenbol P., Willis T.D., Todd J.A. Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat. Genet. 2005, 37:1243-1246.
10. Collins F.S., Brooks L.D., Chakravarti A. A DNA polymorphism discovery resource for research on human genetic variation. Genome Res. 1998, 8:1229-1231.
11. Daston G.P., Naciff J.M. Predicting developmental toxicity through toxicogenomics. Birth Defects Res. C Embryo Today 2010, 90:110-117.
12. Davis A.P., Murphy C.G., Saraceni-Richards C.A., Rosenstein M.C., Wiegers T.C., Mattingly C.J. Comparative Toxicogenomics Database: a knowledgebase and discovery tool for chemical-gene-disease networks. Nucleic Acids Res. 2009, 37:D786-D792.
13. Dix D.J., Houck K.A., Martin M.T., Richard A.M., Setzer R.W., Kavlock R.J. The ToxCast program for prioritizing toxicity testing of environmental chemicals. Toxicol. Sci. 2007, 95:5-12.
14. Dixon A.L., Liang L., Moffatt M.F., Chen W., Heath S., Wong K.C., Taylor J., Burnett E., Gut I., Farrall M., Lathrop G.M., Abecasis G.R., Cookson W.O. A genome-wide association study of global gene expression. Nat. Genet. 2007, 39:1202-1207.
15. Edwards S.W., Preston R.J. Systems biology and mode of action based risk assessment. Toxicol. Sci. 2008, 106:312-318.
16. Eichler E.E., Nickerson D.A., Altshuler D., Bowcock A.M., Brooks L.D., Carter N.P., Church D.M., Felsenfeld A., Guyer M., Lee C., Lupski J.R., Mullikin J.C., Pritchard J.K., Sebat J., Sherry S.T., Smith D., Valle D., Waterston R.H. Completing the map of human genetic variation. Nature 2007, 447:161-165.
17. Eubanks M. Biomarkers: the clues to genetic susceptibility. Environ. Health Perspect. 1994, 102(50-53):56.
18. Ewart-Toland A., Balmain A. The genetics of cancer susceptibility: from mouse to man. Toxicol. Pathol. 2004, 32(Suppl 1):26-30.
19. Fry R.C., Svensson J.P., Valiathan C., Wang E., Hogan B.J., Bhattacharya S., Bugni J.M., Whittaker C.A., Samson L.D. Genomic predictors of interindividual differences in response to DNA damaging agents. Genes Dev. 2008, 22:2621-2626.
20. Ginsberg G., Smolenski S., Neafsey P., Hattis D., Walker K., Guyton K.Z., Johns D.O., Sonawane B. The influence of genetic polymorphisms on population variability in six xenobiotic-metabolizing enzymes. J. Toxicol. Environ. Health 2009, 12:307-333.
21. Goh K.I., Cusick M.E., Valle D., Childs B., Vidal M., Barabasi A.L. The human disease network. Proc. Natl Acad. Sci. USA 2007, 104:8685-8690.
22. Gohlke J.M., Thomas R., Zhang Y., Rosenstein M.C., Davis A.P., Murphy C., Becker K.G., Mattingly C.J., Portier C.J. Genetic and environmental pathways to complex diseases. BMC Syst. Biol. 2009, 3:46.
23. Goldstein D.B. Common genetic variation and human traits. N. Engl. J. Med. 2009, 360:1696-1698.
24. Gonzalez F.J., Shah Y.M. PPARalpha: mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. Toxicology 2008, 246:2-8.
25. Gutenkunst R.N., Hernandez R.D., Williamson S.H., Bustamante C.D. Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genet. 2009, 5:e1000695.
26. Guyton K.Z., Barone S., Brown R.C., Euling S.Y., Jinot J., Makris S. Mode of action frameworks: a critical analysis. J. Toxicol. Environ. Health 2008, 11:16-31.
27. Hamadeh H.K., Bushel P.R., Jayadev S., DiSorbo O., Bennett L., Li L., Tennant R., Stoll R., Barrett J.C., Paules R.S., Blanchard K., Afshari C.A. Prediction of compound signature using high density gene expression profiling. Toxicol. Sci. 2002, 67:232-240.
28. Hamadeh H.K., Bushel P.R., Jayadev S., Martin K., DiSorbo O., Sieber S., Bennett L., Tennant R., Stoll R., Barrett J.C., Blanchard K., Paules R.S., Afshari C.A. Gene expression analysis reveals chemical-specific profiles. Toxicol. Sci. 2002, 67:219-231.
29. Ionita-Laza I., Lange C., N M.L. Estimating the number of unseen variants in the human genome. Proc. Natl Acad. Sci. USA 2009, 106:5008-5013.
30. Jayapal M., Bhattacharjee R.N., Melendez A.J., Hande M.P. Environmental toxicogenomics: a post-genomic approach to analysing biological responses to environmental toxins. Int. J. Biochem. Cell Biol. 2010, 42:230-240.
31. Judson R., Richard A., Dix D., Houck K., Elloumi F., Martin M., Cathey T., Transue T.R., Spencer R., Wolf M. ACToR--Aggregated Computational Toxicology Resource. Toxicol. Appl. Pharmacol. 2008, 233(1):7-13.
32. Judson R., Richard A., Dix D.J., Houck K., Martin M., Kavlock R., Dellarco V., Henry T., Holderman T., Sayre P., et al. The toxicity data landscape for environmental chemicals. Environ. Health Perspect. 2009, 117(5):685-695.
33. Judson R. Public databases supporting computational toxicology. J. Toxicol. Environ. Health 2010, 13:218-231.
34. Judson R.S., Houck K.A., Kavlock R.J., Knudsen T.B., Martin M.T., Mortensen H.M., Reif D.M., Rotroff D.M., Shah I., Richard A.M., Dix D.J. In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project. Environ. Health Perspect. 2010, 118(4):485-492.
35. Klaunig J.E., Babich M.A., Baetcke K.P., Cook J.C., Corton J.C., David R.M., DeLuca J.G., Lai D.Y., McKee R.H., Peters J.M., Roberts R.A., Fenner-Crisp P.A. PPARalpha agonist-induced rodent tumors: modes of action and human relevance. Crit. Rev. Toxicol. 2003, 33:655-780.
36. Klein T.E., Chang J.T., Cho M.K., Easton K.L., Fergerson R., Hewett M., Lin Z., Liu Y., Liu S., Oliver D.E., Rubin D.L., Shafa F., Stuart J.M., Altman R.B. Integrating genotype and phenotype information: an overview of the PharmGKB project. Pharmacogenetics Research Network and Knowledge Base. The Pharmacogenomics Journal 2001, 1:167-170.
37. Knudsen T.B., Martin M.T., Kavlock R.J., Judson R.S., Dix D.J., Singh A.V. Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA's ToxRefDB. Reproductive Toxicology (Elmsford, N.Y.) 2009, 28:209-219.
38. Krewski D., Acosta D., Andersen M., Anderson H., Bailar J.C., Boekelheide K., Brent R., Charnley G., Cheung V.G., Green S., Kelsey K.T., Kerkvliet N.I., Li A.A., McCray L., Meyer O., Patterson R.D., Pennie W., Scala R.A., Solomon G.M., Stephens M., Yager J., Zeise L. Toxicity testing in the 21st century: a vision and a strategy. J. Toxicol. Environ. Health 2010, 13:51-138.
39. Kudaravalli S., Veyrieras J.B., Stranger B.E., Dermitzakis E.T., Pritchard J.K. Gene expression levels are a target of recent natural selection in the human genome. Mol. Biol. Evol. 2009, 26:649-658.
40. Lan Q., Zhang L., Shen M., Jo W.J., Vermeulen R., Li G., Vulpe C., Lim S., Ren X., Rappaport S.M., Berndt S.I., Yeager M., Yuenger J., Hayes R.B., Linet M., Yin S., Chanock S., Smith M.T., Rothman N. Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity. Carcinogenesis 2009, 30:50-58.
41. LePage D.F., Conlon R.A. Animal models for disease: knockout, knock-in, and conditional mutant mice. Meth. Mol. Med. 2006, 129:41-67.
42. Linghu B., Snitkin E.S., Hu Z., Xia Y., Delisi C. Genome-wide prioritization of disease genes and identification of disease-disease associations from an integrated human functional linkage network. Genome Biol. 2009, 10:R91.
43. Livingston R.J., von Niederhausern A., Jegga A.G., Crawford D.C., Carlson C.S., Rieder M.J., Gowrisankar S., Aronow B.J., Weiss R.B., Nickerson D.A. Pattern of sequence variation across 213 environmental response genes. Genome Res. 2004, 14:1821-1831.
44. Lohmueller K.E., Bustamante C.D., Clark A.G. The effect of recent admixture on inference of ancient human population history. Genetics 2010, 185:611-622.
45. Manolio T.A., Collins F.S. The HapMap and genome-wide association studies in diagnosis and therapy. Annu. Rev. Med. 2009, 60:443-456.
46. Martin M.T., Judson R.S., Reif D.M., Kavlock R.J., Dix D.J. Profiling chemicals based on chronic toxicity results from the U.S. EPA ToxRef Database. Environ. Health Perspect. 2009, 117:392-399.
47. Martin M.T., Mendez E., Corum D.G., Judson R.S., Kavlock R.J., Rotroff D.M., Dix D.J. Profiling the reproductive toxicity of chemicals from multigeneration studies in the toxicity reference database. Toxicol. Sci. 2009, 110:181-190.
48. Mattingly C.J. Chemical databases for environmental health and clinical research. Toxicol. Lett. 2009, 186(1):62-65.
49. McGary K.L., Park T.J., Woods J.O., Cha H.J., Wallingford J.B., Marcotte E.M. Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc. Natl Acad. Sci. USA 2010, 107:6544-6549.
50. Miller R.T., Willson T.M. Regulation of xenobiotic metabolism by orphan nuclear receptors. Toxicol. Pathol. 2001, 29:3-5.
51. Moore K.J. Utilization of mouse models in the discovery of human disease genes. Drug Discov. Today 1999, 4:123-128.
52. Mortensen, H.M., 2008. Genetic variation at the N- acetyltransferase (NAT) genes in global human populations. Doctoral Dissertation: Department of Biology. University of Maryland, College Park.
53. Mortensen, H. M., Dix, D., Houck, K., Kavlock, R., Shah, I., Judson, R., (2009). The ToxCast™ pathway database identifying toxicity signatures and potential modes of action from chemical screening data. Society of Toxicology, The Toxicologist, pp. Poster #1090.
54. Mortensen, H. M., Dix, D., Houck, K., Kavlock, R., Shah, I., Judson, R., (2010). Identifying functionally linked gene modules within biological pathways assessed by ToxCast in vitro assays. Society of Toxicology, The Toxicologist, pp. Poster #212.
55. Mortensen H.M., Froment A., Lema G., Bodo J.M., Ibrahim M., Nyambo T.B., Omar S.A., Tishkoff S.A. Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations. Pharmacogenomics 2011, 12(11):1545-1558.
56. Myers S., Bottolo L., Freeman C., McVean G., Donnelly P. A fine-scale map of recombination rates and hotspots across the human genome. Science 2005, 310:321-324.
57. National Research Council (2000). Scientific Frontiers in Developmental Toxicology and Risk Assessment. (Board on Environmental Studies and Toxicology, Committee on Developmental Toxicology, Ed.). National Academy of Sciences.
58. National Research Council (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. In (Committee on Toxicity Testing and Assessment of Environmental Agents, Ed.). National Academy of Sciences.
59. National Research Council (2009). Science and Decisions: Advancing Risk Assessment. (N. R. C. Committee on Improving Risk Analysis Approaches Used by the U.S. EPA, Ed.). National Academy of Sciences.
60. National Research Council (2010). Toxicity Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary(Standing Committee on Risk Analysis Issues and Reviews. Ellen Mantus, Rapporteur.), Washington, DC.
61. Nielsen R., Williamson S., Kim Y., Hubisz M.J., Clark A.G., Bustamante C. Genomic scans for selective sweeps using SNP data. Genome Res. 2005, 15:1566-1575.
62. Nitsch D., Goncalves J., Ojeda F., deMoor B., Moreau Y. Candidate gene prioritization by network analysis of differential expression using machine learning approaches. BMC Bioinform. 2010, 11:460.
63. Patel C.J., Bhattacharya J., Butte A.J. An Environment-Wide Association study (EWAS) on type 2 diabetes mellitus. PLoS ONE 2010, 5:e10746.
64. Peters, J.M., Cheung, C., Gonzalez, F.J., 2005. Peroxisome proliferator-activated receptor-alpha and liver cancer: where do we stand? J. Mol. Med. (Berlin, Germany) 83, 774-785.
65. Peters J.M., Hollingshead H.E., Gonzalez F.J. Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in gastrointestinal tract function and disease. Clin. Sci. (Lond) 2008, 115:107-127.
66. Phillips T.J., Belknap J.K., Hitzemann R.J., Buck K.J., Cunningham C.L., Crabbe J.C. Harnessing the mouse to unravel the genetics of human disease. Genes Brain Behav. 2002, 1:14-26.
67. Pritchard J.K., Donnelly P. Case-control studies of association in structured or admixed populations. Theor. Popul. Biol. 2001, 60:227-237.
68. Risch N., Merikangas K. The future of genetic studies of complex human diseases. Science 1996, 273:1516-1517.
69. Ross D., Zhou H. Relationships between metabolic and non-metabolic susceptibility factors in benzene toxicity. Chem.-Biol. Interact. 2010, 184:222-228.
70. Rothman N., Smith M.T., Hayes R.B., Traver R.D., Hoener B., Campleman S., Li G.L., Dosemeci M., Linet M., Zhang L., Xi L., Wacholder S., Lu W., Meyer K.B., Titenko-Holland N., Stewart J.T., Yin S., Ross D. Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C→T mutation and rapid fractional excretion of chlorzoxazone. Cancer Res. 1997, 57:2839-2842.
71. Sabeti P.C., Varilly P., Fry B., Lohmueller J., Hostetter E., Cotsapas C., Xie X., Byrne E.H., McCarroll S.A., Gaudet R., Schaffner S.F., Lander E.S., Frazer K.A., Ballinger D.G., Cox D.R., Hinds D.A., Stuve L.L., Gibbs R.A., Belmont J.W., Boudreau A., Hardenbol P., Leal S.M., Pasternak S., Wheeler D.A., Willis T.D., Yu F., Yang H., Zeng C., Gao Y., Hu H., Hu W., Li C., Lin W., Liu S., Pan H., Tang X., Wang J., Wang W., Yu J., Zhang B., Zhang Q., Zhao H., Zhao H., Zhou J., Gabriel S.B., Barry R., Blumenstiel B., Camargo A., Defelice M., Faggart M., Goyette M., Gupta S., Moore J., Nguyen H., Onofrio R.C., Parkin M., Roy J., Stahl E., Winchester E., Ziaugra L., Altshuler D., Shen Y., Yao Z., Huang W., Chu X., He Y., Jin L., Liu Y., Shen Y., Sun W., Wang H., Wang Y., Wang Y., Xiong X., Xu L., Waye M.M., Tsui S.K., Xue H., Wong J.T., Galver L.M., Fan J.B., Gunderson K., Murray S.S., Oliphant A.R., Chee M.S., Montpetit A., Chagnon F., Ferretti V., Leboeuf M., Olivier J.F., Phillips M.S., Roumy S., Sallee C., Verner A., Hudson T.J., Kwok P.Y., Cai D., Koboldt D.C., Miller R.D., Pawlikowska L., et al. Genome-wide detection and characterization of positive selection in human populations. Nature 2007, 449:913-918.
72. Simmons D. The use of animal models in studying genetic disease: transgenesis and induced mutation. Nature Education 2008, 1.
73. Sone H., Okura M., Zaha H., Fujibuchi W., Taniguchi T., Akanuma H., Nagano R., Ohsako S., Yonemoto J. Profiles of Chemical Effects on Cells (pCEC): a toxicogenomics database with a toxicoinformatics system for risk evaluation and toxicity prediction of environmental chemicals. J. Toxicol. Sci. 2010, 35:115-123.
74. Spitz M.R., Bondy M.L. The evolving discipline of molecular epidemiology of cancer. Carcinogenesis 2010, 31:127-134.
75. Stranger B.E., Forrest M.S., Clark A.G., Minichiello M.J., Deutsch S., Lyle R., Hunt S., Kahl B., Antonarakis S.E., Tavare S., Deloukas P., Dermitzakis E.T. Genome-wide associations of gene expression variation in humans. PLoS Genet. 2005, 1:e78.
76. Stranger B.E., Nica A.C., Forrest M.S., Dimas A., Bird C.P., Beazley C., Ingle C.E., Dunning M., Flicek P., Koller D., Montgomery S., Tavare S., Deloukas P., Dermitzakis E.T. Population genomics of human gene expression. Nat. Genet. 2007, 39:1217-1224.
77. Tishkoff S.A., Reed F.A., Friedlaender F.R., Ehret C., Ranciaro A., Froment A., Hirbo J.B., Awomoyi A.A., Bodo J.M., Doumbo O., Ibrahim M., Juma A.T., Kotze M.J., Lema G., Moore J.H., Mortensen H., Nyambo T.B., Omar S.A., Powell K., Pretorius G.S., Smith M.W., Thera M.A., Wambebe C., Weber J.L., Williams S.M. The genetic structure and history of Africans and African Americans. Science 2009, 324:1035-1044.
78. Tishkoff S.A., Reed F.A., Ranciaro A., Voight B.F., Babbitt C.C., Silverman J.S., Powell K., Mortensen H.M., Hirbo J.B., Osman M., Ibrahim M., Omar S.A., Lema G., Nyambo T.B., Ghori J., Bumpstead S., Pritchard J.K., Wray G.A., Deloukas P. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 2007, 39:31-40.
79. US Environmental Protection Agency (2002). Toxicological Review of Benzene (NonCancer Effects) (In Support of Summary Information on the Integrated Risk Information System (IRIS), Washington, DC.
80. US Environmental Protection Agency (2005). Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens. (Risk Assessment Forum, Ed.), Washington, DC USA.
81. Voight B.F., Kudaravalli S., Wen X., Pritchard J.K. A map of recent positive selection in the human genome. PLoS Biol. 2006, 4:e72.
82. Wan J., Shi J., Hui L., Wu D., Jin X., Zhao N., Huang W., Xia Z., Hu G. Association of genetic polymorphisms in CYP2E1, MPO, NQO1, GSTM1, and GSTT1 genes with benzene poisoning. Environ. Health Perspect. 2002, 110:1213-1218.
83. Watanabe K.H., Andersen M.E., Basu N., Carvan M.J., Crofton K.M., King K.A., Sunol C., Tiffany-Castiglioni E., Schultz I.R. Defining and modeling known adverse outcome pathways: domoic acid and neuronal signaling as a case study. Environmental toxicology and chemistry / SETAC 2011, 30:9-21.
84. Weir B.S., Cardon L.R., Anderson A.D., Nielsen D.M., Hill W.G. Measures of human population structure show heterogeneity among genomic regions. Genome Res. 2005, 15:1468-1476.
85. Wiegers T.C., Davis A.P., Cohen K.B., Hirschman L., Mattingly C.J. Text mining and manual curation of chemical-gene-disease networks for the comparative toxicogenomics database (CTD). BMC Bioinform. 2009, 10:326.
86. Wild C.P. Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev 2005, 14:1847-1850.
87. Wilson S.H., Olden K. The Environmental Genome Project: phase I and beyond. Mol. Interv. 2004, 4:147-156.
88. Young L.J. Oxytocin and vasopressin as candidate genes for psychiatric disorders: lessons from animal models. Am. J. Med. Genet. 2001, 105:53-54.
89. Zanger U. Pharmacogenetics-challenges and opportunities ahead. Frontiers in Pharmacology:Opinion Article 2010, 1.
90. Zhang L., McHale C.M., Rothman N., Li G., Ji Z., Vermeulen R., Hubbard A.E., Ren X., Shen M., Rappaport S.M., North M., Skibola C.F., Yin S., Vulpe C., Chanock S.J., Smith M.T., Lan Q. Systems biology of human benzene exposure. Chem.-Biol. Interact. 2010, 184:86-93.
91. Zhao H., Jin S., Fan F., Fan W., Tong T., Zhan Q. Activation of the transcription factor Oct-1 in response to DNA damage. Cancer Res. 2000, 60:6276-6280.