Index

A

AddHealth survey, 9, 191, 194

Adipsin gene, 264

Adolescents

datasets, 190, 191

pregnancy, 28

smoking, 71

Adoption studies, 29, 121, 254

ADRA1, ADRA2 genes, 305

ADRB1, ADRB2 genes, 305

Adrenergic receptors, 137

Adrenocorticotropin, 143, 298, 299

Affymetrix, 124

African Americans, 39.

See also Race/ethnicity

health disparities, 98, 102-103

multiple jeopardy hypothesis, 103

obesity, 241, 244, 251, 252, 253, 267

stress, 76

TV programming, 252

Agouti signaling proteins, 73, 257, 258

AGTR1 gene, 305

Alcohol use and alcoholism, 15, 33, 37, 78, 79, 140, 145, 167, 172

Alpha-1 antitrypsin deficiency, 206-207, 208

α-Melanocyte stimulating hormone, 257, 258

Alzheimer’s disease, 46, 61, 77-78, 185, 214

American Association of Medical Colleges, 195

American Association of Universities, 195

Americans with Disabilities Act, 207

Anger and hostility, 57, 298

Animal research

autoimmune disease, 132, 142-144

biomedical research, 133-134

cancer, 149

causality in, 132, 137

chickens, 144

context, pleitropy, and lifetime fitness, 137-139

criteria for suitable models, 149-150

deer mice (Peromyscus maniculatus), 134

definitions from, 136-139

early life experience, 139-140, 145

eating behavior, 135

ecological context, 133, 150

epidemiological research, 330

ethological approach, 134, 150

experimental allergic encephalomyelitis, 143-144

future issues, 149-150

gene-social environment interactions, 76, 133, 134, 136, 137, 139-150



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Index A Alzheimer’s disease, 46, 61, 77-78, 185, 214 AddHealth survey, 9, 191, 194 American Association of Medical Colleges, Adipsin gene, 264 195 Adolescents American Association of Universities, 195 datasets, 190, 191 Americans with Disabilities Act, 207 pregnancy, 28 Anger and hostility, 57, 298 smoking, 71 Animal research Adoption studies, 29, 121, 254 autoimmune disease, 132, 142-144 ADRA1, ADRA2 genes, 305 biomedical research, 133-134 ADRB1, ADRB2 genes, 305 cancer, 149 Adrenergic receptors, 137 causality in, 132, 137 Adrenocorticotropin, 143, 298, 299 chickens, 144 Affymetrix, 124 context, pleitropy, and lifetime fitness, African Americans, 39. See also Race/ 137-139 ethnicity criteria for suitable models, 149-150 health disparities, 98, 102-103 deer mice (Peromyscus maniculatus), multiple jeopardy hypothesis, 103 134 obesity, 241, 244, 251, 252, 253, 267 definitions from, 136-139 stress, 76 early life experience, 139-140, 145 TV programming, 252 eating behavior, 135 Agouti signaling proteins, 73, 257, 258 ecological context, 133, 150 AGTR1 gene, 305 epidemiological research, 330 Alcohol use and alcoholism, 15, 33, 37, 78, ethological approach, 134, 150 79, 140, 145, 167, 172 experimental allergic encephalomyelitis, Alpha-1 antitrypsin deficiency, 206-207, 143-144 208 future issues, 149-150 α-Melanocyte stimulating hormone, 257, gene-social environment interactions, 76, 258 133, 134, 136, 137, 139-150 351

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352 INDEX generalizability to humans, 133-134, Behavioral factors. See also Eating 135-136 behaviors; Health risk behaviors; genetics, 73, 136, 142-144 Physical inactivity; Tobacco use house sparrows, 133 context for interaction studies, 22, 125 immune function, 134, 136-137, 138- CVD, 57, 58, 70, 73 139, 141, 143-144 obesity, 245-251 knockout models, 142, 149, 330 peer and family influences, 71 limitations, 135-136 and psychological response and mediating variables, 137 physiological processes, 116-122 modeling known interactions and β2-AR, β3-AR genes, 137, 257, 264, 305 diseases in humans, 133-134 β-Endorphins, 301 moderating variables, 137 β-Thalassemia, 54-55, 101, 284 Morris water maze, 135 Binge Eating Disorder, 261 nicotine addiction, 70, 79 Biochemical System Theory, 123 nonhuman primates, 133, 140, 141, Biochemical systems and processes. See also 142, 145-146 Metabonomics; Proteomics nontraditional animal models, 134 affiliative behavior and, 36, 145 obesity, 73, 267 genomic information embedded in, 114- physiology, 136-137 116 psychosocial traits, 133, 135-136, 144 modeling, 123 rationale, 132-133 psychological response to social factors recommendations, 7, 150 and, 21, 116-122 rodent models, 133, 135, 138, 140, 141- stress and, 117-122 142, 144, 145-146, 147, 149 Bioinformatics, 51 role, 132-136 Biologic interaction, 311, 317, 322 side-blotch lizards, 138-139 Biology, hierarchical view, 123 social affiliation and support, 141, 142 Biomedical model, 281-282 social isolation, 133, 138, 141-142 Biomedical research, 15, 18, 133-134 social status, 133, 144-146 Biomolecular Interaction Network social stressors, 145, 146-147 Database, 124 stress responsivity, 135, 137, 142-144, Biopsychosocial model, 282, 283, 297 145, 146-148 Birth defects, 47 temperament, 140-141 Blood lead levels, 27 Antioxidant regulatory element, 51 Bloom syndrome, 101 Apolipoprotein E protein polymorphisms, BMP6 gene, 288 61, 76, 214 Body Mass Index (BMI), 69, 72, 73, 238, Appetite, 257, 258, 267, 268 250, 252, 253-257, 263. See also Arginine vasopressin, 118, 146 Obesity Arthritis, 143 Bowlby, John, 34 Ashkenazi Jews, 38, 100, 101, 149 Breast cancer, 35, 38, 46, 59, 73, 101, 141, Asthma, 137 149, 174 Ataxia telangiectasia, 149 Atherosclerosis, 118, 119, 147, 298, 302 C Atopic dermatitis, 144 Attention Deficit Hyperactivity Disorder, 80 C-reactive protein, 76, 171-172, 191 Autoimmune disease, 137, 142-144 Cadmium, 114 Canavan’s syndrome, 101 Cancer B animal research, 149 Bardet-Biedel syndrome, 73, 255 biomarkers, 115 Bayesian belief networks, 65 depression and, 80

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353 INDEX gene-environment interaction, 113 environmental influences, 268 genetic susceptibility, 38 n.1, 45, 56, gene-environment interactions, 53, 113, 149 268, 271-272 obesity and, 72 integrative study of, 121-122 physical activity interventions, 73 and life-course patterns of health, 39, smoking and, 70, 310 139-140 social environment and, 35, 38-39 obesity and overweight, 240-241, 244- stress and, 140, 146, 148 245, 247, 248, 252, 261, 267 survival, 72 SES and, 27, 29, 39 temperament, 140 stress and, 117, 118, 120-122, 139, 144, treatment side effects, 73 147, 300 Cardiovascular disease (CVD) Childhood acute lymphoblastic leukemia, behavioral factors, 57, 58, 70, 73 59 depression and, 57, 78, 80-81, 82 Cholecystokinin A receptor, 73 gene-environment interactions, 57-58, Cholesterol, 57, 75-76, 78, 119, 263, 302 75-76, 113, 137 Clinical and Translational Science Award, genetic susceptibility, 45, 56, 57-58, 76 195 immune function and, 137 Clinical Laboratory Improvement life-course perspective, 57 Amendments, 213 moderators of risk, 76, 81 Cluster analysis, 112 obesity and, 72 Cocaine- and amphetamine-stimulated personality and, 77-78 transcript peptide (CART), 258 sex/gender and, 92, 96 Colon cancer, 73, 101 sickle cell disease, 304-305 Communities social environment and, 31, 35, 57, 78, involvement in research protocols, 214- 119 215 stress and, 57, 78, 117, 118, 119, 298, SES/health associations, 18, 26, 30, 31, 304-305 241 Catecholamines, 117, 119, 121, 137, 298, social capital, 36-37 301, 304 Comparative sequence analysis, 51 Caucasians. See also Race/ethnicity Computer Retrieval of Information on A1AT deficiency, 208 Scientific Projects, 195 insulin resistance, 251 Cooperative Study of Sickle Cell Disease, obesity, 155, 261 293, 294 stress, 76 Coping Strategies Questionnaire, 295 thiopurine methyltransferase deficiency, Coronary artery disease, 77, 101, 305 59 Coronary Artery Risk Development in Causality Young Adults (CARDIA) study, 251 in animal research, 132, 137 Coronary heart disease, 39, 61, 92, 98, 298, in epidemiological approaches, 311, 312, 304 316, 319, 330-332 Corticosterone, 142, 143, 146 CGAP Genetic Annotation Initiative SNP Corticotropin releasing factor-like proteins, Database, 64 79 Child development. See Child health and Corticotropin releasing hormone, 117, 146, development 298 Child Feeding Questionnaire, 244 Cortisol, 72, 117, 118, 137, 147, 287-288, Child health and development 299, 300, 301, 303 abused children, 208-209 CpG array-based technology, 114 adopted children, 29 Crohn’s disease, 101 depression, 147 CRP gene, 171-172 eating behavior, 243-244, 247, 248 CYP11B2 gene, 305

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354 INDEX Cystic fibrosis, 101, 209, 219 social supports and, 147 Cytochrome P450 enzymes, 59 stress and, 81-82, 298, 301, 302, 313- Cytochrome P450 genes, 59 314, 328-330 Cytokines, proinflammatory, 299, 302 Developmental behavioral genetics, 271- 272. See also Child health and development D Dexamethasone, 143 Diabetes, 27, 72, 80, 98, 101, 113, 236, Data and databases. See also individual 263 databases Diethylstilbestrol, 114 biological specimens, 192 DNA collection and analysis for this report, damage and repair, 50 223-231 methylation, 113-114, 139 commercial databases, 124 microarray technology, 111-112 creating new datasets, 9, 192-193 sequencing technologies, 49-50 gene expression, 124 Dopamine guidance on data collection, 192 DRD2 gene, 73, 172, 264-265 guide to measures of key concepts, 191- DRD4 gene, 80 192 and eating behavior, 249 informed consent, 191 and nicotine addiction, 71 infrastructure for transdisciplinary transporter, 73 research, 19, 187-194, 220 Drug abuse, 39 merging and integrating, 112 Duke University, 290 metabolic pathways, 124 Duncan Socioeconomic Index, 31, 32 pooling samples, 174 Durkheim, Emile, 34 privacy and confidentiality issues, 191 proteomic, 112, 124 recommendation, 9-10, 194 E replication of, 193-194 review of existing datasets, 188-192 Earnings, 28 security, 211-212, 220-221 Eating behaviors (unhealthy) sharing, 112, 188, 191, 212, 215-216 access to energy-dense foods and, 240, SNP databases, 64, 110 241, 242, 246, 250-251, 252, 269 for systems modeling, 124 animal research, 135 transcriptomic, 112, 124 appetite and, 257, 258, 267, 268 use agreements, 211 and child health and development, 243- Data Quality Act, 212 244, 247, 248 Database of Interacting Proteins, 124 disinhibition trait, 246, 261, 267 Department of Housing and Urban epidemiology, 72 Development, 31 external cues and, 244, 246 Depression fast-food consumption, 72, 241, 242, and cancer, 80 250-251, 270-271 children, 147 food advertising and, 252 and CVD, 57, 78, 80-81, 82 gene-environment interaction, 72-73, gene-environment interactions, 18, 80- 259-260 82, 328-330 genetic influences, 72-73, 243, 257-262, heritability, 81 264-265, 267-268 personality and, 78 health consequences, 72; see also sickle cell disease and, 292, 298 Obesity and smoking, 71 heritability, 259-260, 267 social environment and, 18, 31, 32, 35, hypothalamic response and, 135, 247 147 and mortality, 15

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355 INDEX parent-child feeding dynamics and, 239, Endotoxins, 118 243-245, 269, 271 Energy-dense foods, 240, 241, 242, 246, portion size and, 247, 251, 269 250-251, 252, 269 reinforcing value of food and, 70, 75, Energy expenditure regulation and, 257 76, 172, 248-249, 264-265, 267 Engel, George, 281 research opportunities, 267-268 Enkephalin, 301 restrictive feeding practices, 244-245, 271 Environmental Genome Project, 49, 64 satiation impairment and, 246-248, 267 Environmental genomics, 203 satiety impairment and, 70, 73, 75, 135, Epidemiologic approaches to interactions 244, 248 additive and superadditive models, 7, 8, self-regulation of intake, 244 162, 163-164, 165-166, 168, 170, smoking and, 172 173, 220, 313, 314, 315, 328, 334, social facilitation of, 72, 239, 242-243, 336 259 animal models, 330 socioeconomic status and, 242 biologic interaction, 311, 317, 322 stress and, 301 biological plausibility restriction, 175, style of eating, 135, 249-250 177 taste preferences and, 70, 75, 135, 172, Bonferroni correction, 174-175 250, 257, 259, 268, 269 case-control designs, 163, 168, 169, television viewing and, 252 170, 171, 174, 177, 329, 334, 335 time-extension mechanism and, 243 case-only design, 49, 170, 177, 331-332 traits associated with obesity, 245-251 causal effect (causal contrast), 318, 319- Eating Inventory, 261 322, 328, 330 EcoCyc, 124 causal model, 315-318 Ecological model of health determinants, causal pies heuristic (causal pathways), 18-19 316-317, 319-320, 323, 331 EDN1 gene, 305 causality in, 311, 312, 316, 319, 330- EDNRA gene, 305 332 Education and training of researchers cohort designs, 163, 168, 169, 192-193, conferences, 182 329, 331-332, 334, 335 evaluation of programs, 184 confidence intervals, 334-335 fellowships, 182, 183-184, 185, 190, confidentiality issues, 171 233 confounding and bias, 62, 63, 65, 71, K-12, 181-182, 183 168-169, 170, 171, 172, 174, 257, private support, 187, 190 319, 324, 330, 333, 335 professional development, 184-186 counterfactual (potential outcomes) recommendation, 9, 187, 233 model, 8, 316-328, 330-335, 336 short course approach, 185 definitions of interactions, 7, 161-168, social sciences, 183 176, 220, 312-316, 317 T90 grant, 183-184 designs of studies, 57-58, 166-173, 176- undergraduate, 185-186 177, 331-332 Education quality, 27 exposures, 171-172, 174-175, 311, 316, Educational attainment 319, 323-324 and health, 27-28, 39, 103 false positive test results, 175-176 and smoking, 70 family-based designs, 47, 49, 170-171, Edwards classification, 31 332 Embedded information. See Genomic framework for assessing interaction, information; Metabonomics; 312-316 Proteomics gene-environment interactions, 47, 49, Emotional support, 34 163, 166-173, 174, 311-312, 318, Endothelin-1 gene, 76 329, 330-336

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356 INDEX genetic context, 52, 62, 330-332, 333 Epinephrine, 117, 118, 147, 286, 298, 301, genomic control methods, 169, 170 302, 304 Henle-Koch principles, 310 ERCC2 gene, 50-51 human laboratory (intervention) Erythrocyte adhesion, 302-303 research, 172 Ethical, legal, and social issues independent effect, 162, 165, 312 civil liberties issues, 208-209 individual-level, 164-165 communicating research results, 203-205 infectious disease models, 310 community involvement in research mathematical modeling, 327-330 protocols, 214-215 measurement of environmental factors, data security, 211-212, 220-221 204, 333 disclosure of research results to measurement of interaction, 161-162 participants, 212-213 Mendelian randomization, 171-172 discrimination and stigmatization, 202, modeling innovations, 65 205, 207, 209-210 molecular techniques, 46 environmental regulation, 206-207 multiple comparisons, 175-176, 177, genetic association studies, 51 334-335 genetic screening, 209 multiplicative (log linear) or health care issues, 202, 207 supermultiplicative model, 7, 8, 162, informed consent, 215, 216 163-164, 168, 170, 173, 312-313, insurance coverage, 202, 207 332, 334, 336 intellectual property rights, 203 for nonbinary outcome variables, 172- intervention policies, 205-210, 220 173 lay oversight of protocols, 214-215 permutation testing, 174, 175 “moral hazard,” 206 population stratification, 62, 63, 65, 71, new hypotheses arising from research, 168-169, 170, 171, 172, 257, 335 214 power of, 8, 65, 166, 171, 172, 333-334 privacy and confidentiality concerns, practical applications, 164, 328-330 171, 208, 211-212, 215-216 preventive effects in, 328 protection of research participants, 211 primacy of genetic effect, 331 race/ethnicity as a proxy, 209 protective effects in, 168 recommendations, 11-13, 210, 215-216 psychologic interactions, 317, 328 Eugenics movement, 205 recommendations, 7-8, 177 Experimental allergic encephalomyelitis, reproducibility of results, 48, 63, 175, 143-144 177, 193-194, 204, 257 risk factor framework, 162, 310-311, F 335-336 sample size and power, 8, 65, 166, 169, Familial aggregation studies, 47, 49, 170- 171, 172, 173-174, 177, 192, 193, 171, 332 333-334 Familial dysautonomia, 101 statistical methods and issues, 8, 161-164, Familial hypercholesterolemia, 45, 60-62, 173-175, 177, 311, 312-313, 332 203 sufficient-component cause model, 8, Familial Mediterranean Fever, 101 164-166 Family Research Consortium III, 187, 190 synergy (interaction) assessment, 165, Fast-food consumption, 72, 241, 242, 250- 311, 315, 319, 322-330, 332-333 251, 270-271 temporality, 170 Fetal uncertainties in, 71, 332-335 exposure to stressors, 139 validation, 174 hemoglobin, 284, 285, 289 Epigenetic phenomena, 53, 64, 112, 113- nutrition, 39, 73, 113, 267 114, 139

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357 INDEX G systems approach to modeling health, 123-126, 139 Gaucher disease, 101 temperament and, 35, 37-38, 79, 140- Gel electrophoresis, 115 141, 328 Gender. See Sex/gender tobacco use, 50-51, 70-71 Gene-environment interactions “toxic environments,” 269-270 animal models, 76, 133, 134, 136, 137, Gene expression 139-150 databases, 124 and biological characteristics, 64, 76 defined, 287 biological plausibility, 175, 177 developmental control of, 53, 54-55 cancer, 113 DNA methylation and, 114 correlation model, 270-271 environmental influences, 52, 116-117, counterfactual model, 8, 316-328, 330- 122, 137 335, 336 epigenetic phenomena, 53, 64, 112, 113- CVD, 57-58, 75-76, 113, 137 114, 139 depression and, 18, 80-82, 328-330 fetal nutrition and, 73 developmental consequences, 53, 113, and gene-environment interactions, 52- 268, 271-272 53, 113, 122 eating behaviors and obesity, 72-73, genetic variation in, 6, 110-114, 122 243, 257-262, 264-265, 267-268 and globin, 54-55 epidemiologic approaches, 47, 49, 163, heritability of, 111 166-173, 174, 311-312, 318, 329, in immune response, 288 330-336 life-course perspective, 5-6 gene expression mechanisms and, 52-53, mechanisms, 52-56 113, 122 pharmacogenetics research, 60 intermediate phenotypes as measures of, post-transcriptional control, 53 74-82, 173 serial analysis of, 111 life-course perspective, 39, 47, 113-114 sickle cell disease, 53-56, 284, 287 models of, 166-168 social environment and, 142 moderating, 76, 251, 262, 263-266, stress and, 118, 139, 142, 148, 287-288, 269-270 303, 305 molecular mechanisms, 116-122 transcriptomics technologies, 111-112 for nonbinary outcome variables, 172- Gene-gene interactions, 46, 51-52, 56, 62, 173 236, 257 in obesity, 76, 113, 236, 237-238, 251, Gene Logic, 124 260, 262-272 Gene Ontology Project, 112 personality and, 35, 37, 78-79 Gene products, classification, 112 physical inactivity, 74 Genetic association studies. See also Gene- and proteomics, 122 environment interactions; Gene-gene psychosocial work environment and interactions health and, 37-38 Bayesian networks, 288 racial/ethnic disparities in health, 99- BMI and fat mass, 255-257 101, 102, 104-105 DNA sequencing technologies, 49-50 research challenges and opportunities, eating behaviors, 261-262 39, 40, 64, 266-272 ethical issues, 51 responsivity to environmental factors, genome-wide approach, 111, 174 50-52, 56, 139 HaloChip assay, 111 social isolation, 36, 121, 141-142 population stratification in, 62, 63, 76, statistical modeling, 65 168-169 study design and analysis, 57-58, 166- 173, 176-177, 331-332

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358 INDEX race/ethnicity, 99 population-based measures, 47, 49, 63, reproducibility, 177 71 sickle cell disease, 288, 299 population distribution of variations, SNP profiling, 49-50, 51-52, 58, 110 60-62, 63 transcriptomic studies, 112 research approaches, 44-48 Genetic imprinting, 112, 113 single-gene disorders, 44, 45-46, 47, 48, Genetic linkage analysis 53-56, 63-64, 73, 203-204, 219, databases, 112 255, 257, 260 eating behaviors, 261-262 SNPs, 49-50, 51-52 goal and principle, 47-48 therapeutic response to drugs, 56 sibling pair method, 48 to “toxic environments,” 241 statistical power, 48 Genome Science Education Program, 183 whole-genome, 288 Genomic information Genetic susceptibility. See also Gene- in biochemical systems, 114-116 environment interactions; Gene-gene comparative genomic hybridization interactions assays, 112 adverse drug reactions, 58-60 epigenetic phenomena, 112, 113-114 allelic heterogeneity, 45-46 and gene expression, 6, 110-114, 122 aspects of health influenced by, 56-60 metabonomic technologies, 116 biases in studies, 49 in proteomes, 111, 115 cancer, 38 n.1, 45, 56, 149 social and ethical implications, 203 clinical variability in diseases, 53-56 transcriptomics, 111-112 common disease, common variant Genotype and genotyping hypothesis, 204 array-based, 49, 52-53 CVD, 45, 56, 57-58, 76 interactions with environmental factors, diabetes, 56 113-114 differential risk, 51 pharmacogenetic research, 59-60 etiologic heterogeneity, 46 moderator in gene-environment founder mutations, 60-61, 100 interaction, 269-270 genetic association studies, 49-52, 255- multiplexing arrays, 49 257, 261; see also Genotype and SNP initiatives, 64 genotyping Geographic Information Systems, 269 hierarchy of causes, 311-312, 331 German National Center for Environment life-course perspective, 57, 254 and Health, 124 linkage analysis, 47-48, 255, 261 Glucocorticoids, 117, 118, 121, 137, 139, linkage disequilibrium phenomenon, 62, 145, 146, 298, 301 80, 175 Glutamate, 303 locus heterogeneity, 46 GR gene, 299 mental illness, 56 Growth hormone, 301 molecular epidemiology techniques, 46 GSTM1 gene, 51 multifactorial models, 46, 48, 60, 65 GSTP1 gene, 51 nicotine addiction, 58, 71 GSTT1 gene, 51 obesity, 20, 72-73, 236, 248, 249, 253- Guyton, Arthur, 123 262, 264-266 OMIM statistics, 45 H overeating, 72-73, 243, 257, 259-262 pathway-driven study design, 50 Health determinants penetrance of mutations, 45, 149, 312 life course perspective, 5-6, 21, 22, 25- polygenic models, 44-45, 46, 47, 60, 26, 219, 282 219 systems approach to modeling, 5-6, 17- 19, 123-126

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359 INDEX I Health Insurance Portability and Accountability Act of 1996, Privacy Immune function Rule, 211 animal research, 134, 136-137, 138-141, Health literacy, 28 143-144 Health outcomes. See Mortality; Survival and CVD, 137 and functional recovery; individual gene expression, 288 diseases genetic determinants, 136 Health risk behaviors. See also Eating natural vs. specific immunity, 301, 302 behaviors; Physical inactivity; obesity and, 72 Tobacco use sex/gender and, 93, 94 definitions, 69-70 sickle cell disease and, 283, 287, 300- intermediate phenotypes, 70 302 outcome pathways, 68, 69 smoking and, 70 personality and, 70, 75, 77-79 social environment and, 35, 134, 136- social and cultural environment and, 30, 137, 138-139 37, 71, 237-238 stress and, 21, 117, 118, 119-120, 139- temperament and, 70, 75, 79-80 141, 145, 146-147, 148, 288, 297, Hemochromatosis, 101 298-299, 300-302 Hemoglobin gene expression, 53, 54-55 Impulsive aggression, 18 HER2 gene, 59 Inclusion body myopathy, 101 Heritability Income of BMI and fat mass, 253-255 absolute vs. relative, 30 defined, 46-47. See also Genetic health associations, 29-31 susceptibility measurement, 28-29 of depression, 81 psychological and behavioral of eating behaviors, 259-260, 267 associations, 30 of gene expression, 111 race/ethnicity and, 103 narrow sense vs. broad sense, 253 societal distribution, 31 High school dropouts, 28 tests of associations, 29-30 High/Scope Perry Preschool Project, 28 and weight gain, 241 Hispanics, 103. See also Race/ethnicity Incyte, 124 Histone acetylation, 114 Indians, Asian, 263 HIV infection, 35, 77, 91-92 Infants Home Observation for Measurement of the breastfeeding vs. bottle feeding and, Environment (HOME) system, 268- 243-244 269 mortality, 27 Human DNA Polymorphism Discovery secure attachments, 34 Program, 49 sucking rates and obesity risk, 249, 268 Human Genome Project, 3, 15, 64, 90, 109, weight gain, 267 110, 123, 203 Inflammatory bowel disease, 101 Human Obesity Gene Map, 255, 256 Informational support, 34 Hypertension, 27, 37, 94, 98, 102, 298, Informax, 124 299, 304 Informed consent, 215, 216 Hypospadias, 92 Infrastructure for transdisciplinary research Hypothalamic-pituitary-adrenal (HPA) academic institutional structure and reactivity, 35, 81, 117, 118, 121, policies and, 10-11, 19, 181, 194- 135, 136, 139, 140, 143, 144, 145, 198 247, 297, 298-300, 301, 302, 303, data, 19, 187-194, 220 304 education and training of researchers, 8- Hypothalamic-pituitary-ovarian axis, 301 9, 19, 181-186, 193, 220

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360 INDEX federal and industry research structures defined, 74-75 vs. academic, 197 emotional/motivational states as, 80-82 IDR recommendations applied to, 10, measuring, 75-76 20, 186, 232-235 for obesity, 70, 73, 75, 78, 237 incentives and rewards, 10-11, 20, 193, personality as, 75, 76, 77-79 194-198, 220 for sickle cell disease, 288, 297 MacArthur Network Model, 188-189 temperament as, 75, 76, 79-80 NIH support, 181, 182, 186-187, 194- for tobacco use, 70, 75, 76 198 International HapMap Consortium, 64 P30 Core Grant and, 187 International HapMap Project, 64, 190 peer review, 10, 20, 195, 198-200 Inuit of Greenland, 75-76 private support, 187, 188-189, 190 R01 Research Project Grant and, 186-187 J recommendations, 8-11, 187, 199-200 support mechanisms, 186-187, 272 Job stress Institute for Public Health Genetics, 184 and CVD, 57 Institutional Review Boards, 210-211 effort-reward imbalance model, 37 Instrumental support, 34 job demand-control model, 37 Insulin-like growth factor, 74 Insulin resistance, 70, 72, 251 Interactions. See also Gene-environment K interactions; Gene-gene interactions definitions of, 7, 161-168, 176, 220, Karolinska Institute Human Gene Bi-Allelic 312-316, 317 Sequences Database, 64 framework for assessing, 312-316 Kleinfelter Syndrome, 94 measurement of, 161-162 Kyoto Encyclopedia of Genes and Genomes, Interdisciplinary research (IDR) 112, 124 academic institutional structure, 235 academic institutions’ policies, 233-234 L defined, 3, 19 educators, 233 Laminin, 286 evaluation of programs, 235 Leptin and leptin receptors, 73, 94, 134, 135 funding organizations, 234 Life-course patterns of health journal editors, 234 animal models, 139-140, 145 key conditions for effective programs, Barker hypothesis, 39 194 CVD, 57 MacArthur Network Model, 188-189 determinants, 5-6, 21, 22, 25-26, 219, postdoctoral scholars, 190, 233 282 professional societies, 234 early life experience, 39, 139-140 recommendations for facilitating, 10, 20, in gene-environment interactions, 39, 47, 186, 232-235 113-114 researchers and faculty members, 233 in gene expression, 5-6 students, 232-233 genetic susceptibility to disease, 57, 254 team leaders, 234 obesity, 74, 253, 266-267 Interferon γ, 301 physical inactivity and, 74 INTERHEART Study, 78 poverty, 4-5, 39 Interleukin-1α, 143 race/ethnicity and, 102-103 Interleukin II, 288 sex/gender and, 94 Interleukin-6, 302 social-environment associations, 25-26, Intermediate phenotypes 27, 31, 32, 34, 39, 138 and biological characteristics, 76

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361 INDEX stress and, 118, 145, 300 CVD risk, 76, 81 in study design and analysis, 21, 22 in gene-environment interactions, 76, Lipid metabolism, 119 251, 262, 263-266, 269-270 Lung cancer, 50-51, 310 of obesity, 76, 251, 262, 263-266 Lutheran blood group anitgens, 286 social environment, 262, 263 in stress response, 76, 285, 287-289, 290, 300 M Monamine oxidase A deficiency, 208-209 Mortality MacArthur Foundation, 187, 188 eating behavior and, 15 MacArthur Network Model, 188-189 infant, 27 Machine learning algorithms, 65, 112 obesity and, 72 Major histocompatibility complex, 138 race/ethnicity, 98, 104 Mass spectrometry, 116 SES and, 27, 29, 104 Maternal smoking and, 70 attachment, 36 social and behavioral factors and, 15, education, 27 27, 35 exposure to endocrine disrupting agents, Moving to Opportunity study, 31 92 mRNA transcripts, 111-112, 118, 124, 146, obesity, 267 149, 287 separation, 35, 118, 121, 139 Multidisciplinary research, defined, 3-4, 19 Matrix-assisted laser desorption ionization- Multivariate statistical analysis, 137 time of flight mass, 115 Munich Information Center for Protein MC4R (melanocortin-4 receptor) gene, 257, Sequences, 124 258, 261 Myelosuppression, 59 Media campaigns, 71 Myocardial infarction, 35, 39, 70, 76, 78, Mediation and mediating variables 81, 82, 119 in animal research, 137 in models of interactions, 167 of social environment, 147-148 N of stress reactivity, 139, 147-148, 304 Melanoma, 38 National Association of State Universities Melatonin, 301 and Land Grant Colleges, 195 Metabolic Control Theory, 123 National Bioethics Advisory Commission, Metabolic syndrome, 236 213 Metabolism National Cancer Institute gut flora and, 116 Breast and Prostate Cancer and sex/gender and, 93-94 Hormone-Related Cohort social stressors and, 145, 298 Consortium, 174 Metabonomics, 6, 112, 116, 124 SNP database, 64 Microarray Gene Expression Data Society, National Center for Biotechnology 112 Information, dbSNP database, 64, Midlife health, 27 110 Migration, and genome selection, 109-110, National Health Interview Surveys, 29 263 National Heart, Lung, and Blood Institute Minimum Information About a Microarray Programs in Genomic Applications, 49 Experiment Guidelines, 112 National Human Genome Research Mitochondrial upcoupling proteins, 257 Institute, 15-16, 50 Modeling strategies National Institute of Environmental Health recommendations, 5-7 Sciences, 49 Moderation and moderating variables National Institute of General Medical animal research, 137 Sciences, 16

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362 INDEX National Institutes of Health (NIH), 97-98, BMI and fat mass, 69, 72, 73, 238, 253- 236 255 Certificates of Confidentiality, 211 breastfeeding vs. bottle feeding and, Office of Behavioral and Social Sciences 243-244 Research, 15-16 children, 240-241, 244-245, 247, 248, and transdisciplinary research, 181, 182, 252, 261, 267 186-187, 194-198 conceptual model of interactions, 237-238 National Longitudinal Survey of Youth, 241 critical growth periods for, 266-267 Supplement, 9, 190, 194 energy expenditure regulation and, 257 National Opinion Research Center Study, epidemiology, 72, 236 31 gene-environment interactions, 76, 113, National Research Service Act, 182 236, 237-238, 251, 260, 262-272 National Science Foundation, 181, 182 genetic influences, 20, 72-73, 236, 248, Native Americans, research protocols, 214- 249, 253-262, 264-266 215 health consequences, 72, 236 NEO-Personality Inventory, 77 hypothalamic response and, 247 Neophobia, 140 intermediate phenotypes, 70, 73, 75, 78, Network models, 65, 112 237 Network on Socioeconomic Status and life-course perspective, 74, 253, 266-267 Health, 188-189 macroenvironmental influences, 240- Network theory, 204 242, 268, 269-270 Neurocognitive functioning, 283, 287, 293, maternal, 267 294-295, 297, 303 microenvironmental influences, 242-245 Neuroeconomics, 36 moderating variables, 76, 251, 262, 263- Neuroendocrine regulation, 35 266 Neuropeptide-Y, 257, 258 personality and, 78 NGFI-A transcription factor, 139 physical inactivity and, 74, 240, 251-253 Nickel, 114 race/ethnicity and, 155, 241, 244, 251, Nicotine 252, 253, 261, 267 addiction, 70, 79 research opportunities, 266-272 and cardiovascular function, 70 restrictive feeding practices and, 244- cognitive and autonomic effects, 75 245, 271 patch, 82 social environmental factors and, 20, 27, reward value, 70, 75, 76, 79 72, 236-237, 238-245, 253-255, tolerance and deprivation, 70, 75 263-266 withdrawal and relapse, 79 socioeconomic status and, 239, 241-242, Niemann-Pick disease, 101 264 NMB (Neuromedian-β) gene, 262 “toxic environments,” 237, 239, 240- Norepinephrine, 147, 298, 301, 304 241, 251, 269-270 North Carolina Sickle Cell Center, 290 and underreporting of intakes, 247 NOS1, NOS2, NOS3 genes, 305 Occupational status, 28 NR3C1 gene, 137 child health and, 39 Nuclear magnetic resonance spectroscopy, and health, 31 116 measures of, 31-32 and weight gain, 241 Office of Management and Budget, 97 O Online Mendelian Inheritance in Man (OMIM) statistics, 45 Obesity. See also Eating behaviors; Physical Osteoarthritis, 72 inactivity Ovarian cancer, 149 animal research, 73, 267 Oxytocin, 36, 145 behavioral traits associated with, 245-251

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363 INDEX P Pima Indians, 263-266 Pituitary function, 70 Pain, 286-287, 289, 295-297, 299, 302 Polycystic kidney disease, 46 Pair bonding, 36 Population genetics, 60-62 Panel Study of Income Dynamics, 29, 31 Pound of Prevention Study, 251 Parasitic infections, 137 Poverty. See also Income; Socioeconomic Parent-child feeding dynamics, 239, 243- status/health associations 245, 269, 271 definitions, 30 Path analysis, 123 gender and, 92-93 Pattern recognition methods, 65, 112, 116 health associations, 25 Peptidoglycan polysaccharide, 143 life-course perspective, 4-5, 39 Persian Jews, 100, 101 persistent vs. transient, 39 Personality PPARγ gene, 257 and alcohol consumption, 78 Prader-Willi syndrome, 73, 255 “Big Five” model, 77-78 Preschool education, 28 and CVD, 77-78 Privacy and confidentiality concerns, 171, defined, 77 208, 211-212, 215-216 and depression, 78, 298 Pro-opiomelanocortin (POMC) peptides, gene-environment interaction, 35, 37, 257, 258 78-79 Prolactin, 301 genetic factors, 78 Promoter Database of Saccharomyces and health risk behaviors, 70, 75, 77-79 cerevisiae, 124 as intermediate phenotype, 75, 76, 77-79 Prostate cancer, 174 and obesity, 78 Proteomics, 6, 60, 112, 114, 115, 122, race/ethnicity and, 80 124 sex/gender and, 80 Psoriasis, 77 and social-environmental influences, Psychological/psychiatric disorders and 144-145 behaviors. See also Depression and stress response, 145, 298 occupational status and, 31 and tobacco use, 78 personality and temperament and, 77 Pew Charitable Trust, 182 pharmacogenetics research, 59 Pharmacogenetics, 56, 58-60, 203 SES of communities and, 18 Phenylketonuria, 45, 167, 318 social connectedness and, 35 Physical activity Psychoneuroimmunology, 35 defined, 69 Psychosocial traits protective effects, 71, 73, 119 animal models, 133, 135-136, 144 recommended, 69, 73 Psychosocial work environment/health Physical inactivity associations. See also Job stress animal studies, 74 biases in, 37-38 epidemiology, 73-74 gene-environment interactions, gene-environment interactions, 74 37-38 genetic influences, 74 evidence of, 25, 37-38 health consequences, 15, 73-74 measures of, 31, 32, 37 life-course perspective, 74 occupational status and, 31, 32 nonexercise activity thermogenesis, 252- reciprocal relationships, 37 253, 268 and obesity, 74, 240, 251-253 Q research opportunities, 268 social/cultural environment and, 27, 72, Quebec Family study, 262 74, 240, 241, 242 Quebec Overfeeding Study, 269 television, video recorders and computers and, 240, 251-252

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364 INDEX R pathways, 71 stress response, 298, 303 Race/ethnicity transporter (5HTTLPR) gene, 59, 76, and ancestral origin, 98, 99 78, 80, 81-82, 145, 146, 147, 261, confounding issues, 98 305, 328-330 context for research, 96-98, 99, 125- Sex/gender 126, 219 animal research, 93 definition, 97 and body weight and fat stores, 93-94 gene-environment interactions, 99-101, context for interactions research, 94, 102, 104-105 125-126, 219 and genetic variation, 38 n.1, 61, 97, and CVD, 92, 96 99-104 definitions, 91 health disparities and, 90-91, 98-104 and delivery of health care, 92 life-course perspective, 102-103 and energy metabolism, 93-94 and mortality, 98, 104 and health, 90, 91-96 and personality, 80 and heritability of food intake, 259 and SES, 27, 103-104 and immune response, 93, 94 SNP markers of phenotypic variation, independent dimensions in humans, 95 99-101 and life-course patterns of health, 94 and social stressors, 39, 76 and personality, 80 Racism and discrimination, 39 and poverty, 92-93 Random forest methods, 65 and social environment, 92-93 Renal function, 70, 305 and stress, 93 Renin-angiotensin-aldosterone system, 299, synergistic effects of biology and gender 304 relations, 91-92 Reproductive dysfunction, 138, 118 variants, 95, 96 Research. See Epidemiologic approach; Sexual dimorphism, 94 Infrastructure; Interdisciplinary Shotgun proteomic analysis, 115 research; Transdisciplinary Sickle cell disease interactions research α-thalassemia, 285, 288, 289-290 Rett syndrome, 113 ancestral origin and, 100 Rheumatic diseases, 144 β-thalassemia, 54-55, 101, 284, 291, Risk behaviors. See Health risk behaviors; 292, 295, 296 specific behaviors cardiovascular and renal response, 286, Risk prevention programs, 82 287, 304-305 Rosetta, 124 clinical manifestations, 56, 286-287 definitions, 284 epistatic or modifier genes, 285, 287- S 289, 290, 300 erythrocyte adhesion to endothelial cells, Satiation, 246-248, 267 285, 286, 302-303 Satiety, 70, 73, 75, 135, 244, 248 etiology, 283-284 Scale-free networks, 65 and family functioning, 293 Science Education Partnership Awards, 182- fetal hemoglobin, 284, 285, 289 183 gene expression, 45, 53-56, 284, 287 Sedentary lifestyle. See Physical inactivity HPA activation and, 298-300 Selective serotonin re-uptake inhibitors hydroxyurea treatment, 289 (SSRIs), 59 and immune response, 283, 287, 300- SELP gene, 288 302 Sephardi Jews, 100, 101 individual differences in severity, 282- Serotonin 283, 287-289 central nervous system responsivity, 18

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365 INDEX intermediate phenotype, 288, 297 macroenvironmental variables, 240-242, maternal adjustment, 291-292 268, 269-270 and neurocognitive functioning, 283, measures of, 204, 268-271 287, 293, 294-295, 297, 303 mediators of effects of, 147-148 pain, 286-287, 289, 295-297, 299, 302 microenvironmental variables, 242-245 pathogenesis, 284 moderating effects, 262, 263 pathophysiology, 55-56, 283, 285-286 and mortality, 15, 27, 35 psychological adjustment to, 287, 290- natural policy experiments, 27-28 294, 295 and obesity, 20, 27, 72, 236-237, 238- resistance to malarial infection, 61, 100 245, 253-255, 263-266 severity, 54-55, 284-285, 286, 287, 289, and personality, 144-145 295 population density, 138 stress and, 20, 283, 287-288, 292, 297- research opportunities, 39, 268-269 305 and sedentary lifestyle, 27, 72, 74, 240, and stroke, 286, 287, 288-289, 294, 305 241, 242 sympathetic nervous system activation sex/gender and, 92-93 and, 298, 302 shared vs. unshared, 253-255, 267, 269 trait, 53-54, 284 stressful, 20, 25, 30-31, 32, 39, 57, 78, Sickness behavior, 301 117-122, 138-139, 145, 146-147, Silicon Genetics, 124 300, 312-313, 146-147 Simian immunodeficiency virus, 141 and temperament, 140-141 Single nucleotide polymorphisms (SNPs), “toxic environments,” 237, 239, 240- 49-50, 51-52, 58, 62, 64, 99-101, 241, 251, 269-270 110, 168-169 variables affecting health, 26, 240-245 SLC6A3 gene, 264-265 Social attachment, 79 Sleep patterns, 301 Social capital, 36-37 Social and cultural environment. See also Social control, 37 Psychosocial work environment; Social isolation, 36, 121, 133, 138, 141-142 Social networks; Social support; Social mobility, 32 Socioeconomic status Social networks/social supports and health animal research, 36, 139-147 animal research, 141, 142, 147 aspects of health influenced, 38-39, 57, 78 bidirectional relationships, 35, 147 and biological processes, 36, 116-122 biological basis, 36 and cancer, 35, 38-39 causality, 35-36 context for interactions research, 5, 6-7, community-level, 36-37 21, 25-26, 125 confounding bias, 35 cumulative effects, 39 definitions and types, 34 and CVD, 31, 35, 57, 78, 119 and depression, 147 defining, 21, 25-26, 238-239 evidence of health effects, 25, 34-37 and depression, 18, 31, 32, 35, 147 and health outcomes, 39 dynamic trajectories, 39 and immune function, 35 early life experience, 139-140 and incidence of disease, 39 evidence of health associations, 26-38 measures of, 34-35 and gene expression, 142 naturally occurring vs. strangers, 36 generational effects, 39 negative, 35 genetic selection of, 113-114 status and, 32, 302 and health risk behaviors, 30, 37, 71, temperament or personality and, 35 237-238 Social status. See also Occupational status; and immune response, 35, 134, 136- Socioeconomic status 137, 138-139 animal research, 133, 144-146 life-course, multilevel perspective, 25-26, personality and, 144 27, 31, 32, 34, 39, 138

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366 INDEX Social support. See Social networks and child development, 117, 118, 120- Socioeconomic status/health associations. 122, 139, 144, 147, 300 See also Social status chronic, 118, 139-140, 148, 298, 300, and cancer, 38-39 302, 303, 304 causal pathways, 27, 30, 32 and CVD, 57, 78, 117, 118, 119, 298, causation, 27, 29, 32 302, 304-305 and child health and development, 27, defined, 117, 147-148, 297 29, 39 deleterious coping behaviors, 32, 39 community-level, 18, 26, 30, 31, 241 and depression, 81-82, 298, 301, 302, confounding bias, 27 313-314, 328-330 and eating behavior, 242 early life experiences, 145, 300 economic reserves, 31 and eating behavior, 301 education-related, 15, 25, 27-28 epigenetic programming, 139 flow of resources, 31 and gene expression, 118, 139, 142, income-related, 28-31 148, 287-288, 303, 305 inherited ability and, 29 generational effects, 139 measures of, 26-27 genetic differences in responsivity, 20, moderating effects of, 76, 104, 264 142-144 and mortality, 27, 29, 104 health-promoting effects, 147-148 and obesity, 239, 241-242, 264 HPA axis activation, 297, 298-300, 301, occupational status-related, 31-33 302, 303, 304 psychological disorders and behaviors, and immune function, 21, 117, 118, 18, 30 119-120, 139-141, 145, 146-147, and psychosocial stress, 30-31, 76 148, 288, 297, 298-299, 300-302 race/ethnicity and, 27, 103-104 as intermediate phenotype, 297 relative deprivations, 30-31 job-related, 25 research network, 188-189 life-course perspective, 118, 145, 300 reverse causation, 27, 29, 31-32 and longevity, 118 tests of, 29-30 magnitude of, 148 variations in associations, 38-39 mediating variables, 139, 147-148, 304 wealth, 31, 103-104 moderators of, 76, 285, 287-289, 290, Spotfire, 124 300 Stanilas Family Study, 261 nonsocial factors, 120 Statistical methods. See also Epidemiologic obesity and, 72 approaches to interactions oxytocin and, 36, 145 Bonferroni correction, 174-175 and pain response, 301, 302 confidence intervals, 334-335 personality and, 145, 298 gene expression profiles, 112 physiological responses, 72, 76, 81-82, inferring causality, 137 117-122, 147-148, 287-288 Structural Equation Modeling, 123 psychological response to, 21, 116-122, Stress 302 acute, 148, 302 race/ethnicity and, 39, 76 and alcoholism, 140, 145, 172 research opportunities, 39 allostatic load, 118 SES and, 30-31, 76 animal research, 118, 120, 135, 137, sex/gender and, 93 142-144, 145, 146-148 and sickle cell disease, 20, 283, 287-288, and autoimmune disease, 142-144 292, 297-305 behavioral response, 139, 140 social situations, 20, 25, 30-31, 32, 39, biochemical systems and processes, 117- 57, 78, 117-122, 138-139, 145, 146- 122 147, 300, 312-313 and cancer, 140, 146, 148

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367 INDEX sympathetic nervous system activation, and immune function, 120 297, 298, 301, 302 as intermediate phenotype, 75, 76, 79- temperament and, 120, 140-141 80 Stroke, 35, 39, 82, 98, 119, 135, 286, 287, and social and cultural environment, 288-289, 294, 305 140-141 Structural Equation Modeling, 123 and stress response, 120, 140-141 Study design and analysis. See also and tobacco use, 77, 79, 80 Epidemiologic approaches to traits, 79 interactions Temperament and Character Inventory, 79 life-course perspective, 21, 22 Testicular cancer, 96 Suicide, 18, 81 TGFBR2, TGFBR3 genes, 288 Survival and functional recovery Thiocyanate, 70 cancer, 72, 73 Thiopurine methyltransferase deficiency, 59 obesity and, 72 Thiopurines, 59 personality and, 79 $1,000 Genome Project, 50 social environment and, 38, 39 Thyroid function, 70 Sympathetic nervous system reactivity, 35, TNFα gene, 76 81, 118, 119, 144, 297, 298, 301, Tobacco use 302 advertising and, 79 Systems approach to interactions modeling, bupropion treatment, 172 123-124 cessation, 82, 172 biobehavioral model, 304 and CVD, 57, 58, 70 challenges in development and practice, definition of smoking, 69 124-125 depression and, 71 databases and systems analysis software, epidemiology, 70 124 gene-environment interactions, 50-51, gene-environment interactions, 123-126, 70-71 139 genetic susceptibility to nicotine health determinants, 5-6, 17-19, 123- addiction, 58, 70, 71 126 health consequences, 15, 57, 58, 70 life-course perspective, 282 intermediate phenotypes, 70, 75, 76 recommendations, 125-126 life-course perspective, 74 Systems biology, 123 and lung cancer, 70, 310 System theory, 123 nicotine addiction, 69, 70 personality and, 78 risk factors for initiation, 71 T smoking persistence, 69 social and cultural environment and, 27, Tay-Sachs disease, 45, 101, 219 30, 31, 32, 37, 70-71, 79 Television viewing and social policy, 207 advertising, 252 temperament and, 77, 79, 80 and eating behavior, 252 Transcription Factors Database, 124 and physical inactivity, 240, 251-252 Transcriptomics, 6, 111-112, 124 Temperament Transdisciplinary interactions research. See and ADHD, 80 also Epidemiologic approaches to animal research, 140-141 interactions; Infrastructure for assessment, 79 transdisciplinary research and cancer, 140 barriers to, 19-20 defined, 77 behavioral and psychological variables, gene-social environment interactions, 35, 4, 5, 125 37-38, 79, 140-141, 328 biological signatures, 126 and health risk behaviors, 70, 75, 79-80

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368 INDEX U defined, 4, 19, 220 diversity of groups and settings, 126, UCP1, UCP2, UCP3 genes, 257 220 Ulcerative colitis, 77, 101 funding, 272 University of Washington, Seattle, 184 genetic factors, 4, 125 U.S. Department of Health and Human hiring, promotion, and tenure policies Services, 211 and, 195-196 life-course perspective, 4-5, 94, 125 minority subjects in, 97-98 V physiological measures and pathways, 4, 22, 125 Vasopressin 1a receptor gene transfer, 142 race/ethnicity context, 4, 96-98, 125-126 recommendations, 3-5, 125-126 sex/gender context, 4, 94, 125-126, 219 W social variables, 4, 21, 25-26, 125 systems modeling approach, 3, 5-6, 123- What Is There, 124 124, 126 Wisconsin Longitudinal Survey, 32 team approach, 186-187, 195-196 Work environment. See Psychosocial work Trust, 36 environment Tumor necrosis factor-alpha, 147 World Health Organization, 69, 72 Tumor suppressor gene, 149 Wright, Sewall, 123 Turner’s syndrome, 91, 95 Twin studies, 47, 71, 81, 254, 255, 258, X 264, 266-267, 269-270, 299 Xenobiotics, 114 XRCCI gene, 50-51