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

generalizability to humans, 133-134, 135-136

genetics, 73, 136, 142-144

house sparrows, 133

immune function, 134, 136-137, 138-139, 141, 143-144

knockout models, 142, 149, 330

limitations, 135-136

mediating variables, 137

modeling known interactions and diseases in humans, 133-134

moderating variables, 137

Morris water maze, 135

nicotine addiction, 70, 79

nonhuman primates, 133, 140, 141, 142, 145-146

nontraditional animal models, 134

obesity, 73, 267

physiology, 136-137

psychosocial traits, 133, 135-136, 144

rationale, 132-133

recommendations, 7, 150

rodent models, 133, 135, 138, 140, 141-142, 144, 145-146, 147, 149

role, 132-136

side-blotch lizards, 138-139

social affiliation and support, 141, 142

social isolation, 133, 138, 141-142

social status, 133, 144-146

social stressors, 145, 146-147

stress responsivity, 135, 137, 142-144, 145, 146-148

temperament, 140-141

Antioxidant regulatory element, 51

Apolipoprotein E protein polymorphisms, 61, 76, 214

Appetite, 257, 258, 267, 268

Arginine vasopressin, 118, 146

Arthritis, 143

Ashkenazi Jews, 38, 100, 101, 149

Asthma, 137

Ataxia telangiectasia, 149

Atherosclerosis, 118, 119, 147, 298, 302

Atopic dermatitis, 144

Attention Deficit Hyperactivity Disorder, 80

Autoimmune disease, 137, 142-144

B

Bardet-Biedel syndrome, 73, 255

Bayesian belief networks, 65

Behavioral factors.

See also Eating behaviors;

Health risk behaviors;

Physical inactivity;

Tobacco use

context for interaction studies, 22, 125

CVD, 57, 58, 70, 73

obesity, 245-251

peer and family influences, 71

and psychological response and physiological processes, 116-122

β₂-AR, β₃-AR genes, 137, 257, 264, 305

β-Endorphins, 301

β-Thalassemia, 54-55, 101, 284

Binge Eating Disorder, 261

Biochemical System Theory, 123

Biochemical systems and processes.

See also Metabonomics;

Proteomics

affiliative behavior and, 36, 145

genomic information embedded in, 114-116

modeling, 123

psychological response to social factors and, 21, 116-122

stress and, 117-122

Bioinformatics, 51

Biologic interaction, 311, 317, 322

Biology, hierarchical view, 123

Biomedical model, 281-282

Biomedical research, 15, 18, 133-134

Biomolecular Interaction Network Database, 124

Biopsychosocial model, 282, 283, 297

Birth defects, 47

Blood lead levels, 27

Bloom syndrome, 101

BMP6 gene, 288

Body Mass Index (BMI), 69, 72, 73, 238, 250, 252, 253-257, 263.

See also

Obesity

Bowlby, John, 34

Breast cancer, 35, 38, 46, 59, 73, 101, 141, 149, 174

C

C-reactive protein, 76, 171-172, 191

Cadmium, 114

Canavan’s syndrome, 101

Cancer

animal research, 149

biomarkers, 115

depression and, 80

gene-environment interaction, 113

genetic susceptibility, 38 n.1, 45, 56, 149

obesity and, 72

physical activity interventions, 73

smoking and, 70, 310

social environment and, 35, 38-39

stress and, 140, 146, 148

survival, 72

temperament, 140

treatment side effects, 73

Cardiovascular disease (CVD)

behavioral factors, 57, 58, 70, 73

depression and, 57, 78, 80-81, 82

gene-environment interactions, 57-58, 75-76, 113, 137

genetic susceptibility, 45, 56, 57-58, 76

immune function and, 137

life-course perspective, 57

moderators of risk, 76, 81

obesity and, 72

personality and, 77-78

sex/gender and, 92, 96

sickle cell disease, 304-305

social environment and, 31, 35, 57, 78, 119

stress and, 57, 78, 117, 118, 119, 298, 304-305

Catecholamines, 117, 119, 121, 137, 298, 301, 304

Caucasians.

See also Race/ethnicity

A1AT deficiency, 208

insulin resistance, 251

obesity, 155, 261

stress, 76

thiopurine methyltransferase deficiency, 59

Causality

in animal research, 132, 137

in epidemiological approaches, 311, 312, 316, 319, 330-332

CGAP Genetic Annotation Initiative SNP Database, 64

Child development. See Child health and development

Child Feeding Questionnaire, 244

Child health and development

abused children, 208-209

adopted children, 29

depression, 147

eating behavior, 243-244, 247, 248

environmental influences, 268

gene-environment interactions, 53, 113, 268, 271-272

integrative study of, 121-122

and life-course patterns of health, 39, 139-140

obesity and overweight, 240-241, 244-245, 247, 248, 252, 261, 267

SES and, 27, 29, 39

stress and, 117, 118, 120-122, 139, 144, 147, 300

Childhood acute lymphoblastic leukemia, 59

Cholecystokinin A receptor, 73

Cholesterol, 57, 75-76, 78, 119, 263, 302

Clinical and Translational Science Award, 195

Clinical Laboratory Improvement Amendments, 213

Cluster analysis, 112

Cocaine- and amphetamine-stimulated transcript peptide (CART), 258

Colon cancer, 73, 101

Communities

involvement in research protocols, 214-215

SES/health associations, 18, 26, 30, 31, 241

social capital, 36-37

Comparative sequence analysis, 51

Computer Retrieval of Information on Scientific Projects, 195

Cooperative Study of Sickle Cell Disease, 293, 294

Coping Strategies Questionnaire, 295

Coronary artery disease, 77, 101, 305

Coronary Artery Risk Development in Young Adults (CARDIA) study, 251

Coronary heart disease, 39, 61, 92, 98, 298, 304

Corticosterone, 142, 143, 146

Corticotropin releasing factor-like proteins, 79

Corticotropin releasing hormone, 117, 146, 298

Cortisol, 72, 117, 118, 137, 147, 287-288, 299, 300, 301, 303

CpG array-based technology, 114

Crohn’s disease, 101

CRP gene, 171-172

CYP11B2 gene, 305

Cystic fibrosis, 101, 209, 219

Cytochrome P450 enzymes, 59

Cytochrome P450 genes, 59

Cytokines, proinflammatory, 299, 302

D

Data and databases.

See also individual databases

biological specimens, 192

collection and analysis for this report, 223-231

commercial databases, 124

creating new datasets, 9, 192-193

gene expression, 124

guidance on data collection, 192

guide to measures of key concepts, 191-192

informed consent, 191

infrastructure for transdisciplinary research, 19, 187-194, 220

merging and integrating, 112

metabolic pathways, 124

pooling samples, 174

privacy and confidentiality issues, 191

proteomic, 112, 124

recommendation, 9-10, 194

replication of, 193-194

review of existing datasets, 188-192

security, 211-212, 220-221

sharing, 112, 188, 191, 212, 215-216

SNP databases, 64, 110

for systems modeling, 124

transcriptomic, 112, 124

use agreements, 211

Data Quality Act, 212

Database of Interacting Proteins, 124

Department of Housing and Urban Development, 31

Depression

and cancer, 80

children, 147

and CVD, 57, 78, 80-81, 82

gene-environment interactions, 18, 80-82, 328-330

heritability, 81

personality and, 78

sickle cell disease and, 292, 298

and smoking, 71

social environment and, 18, 31, 32, 35, 147

social supports and, 147

stress and, 81-82, 298, 301, 302, 313-314, 328-330

Developmental behavioral genetics, 271-272.

See also Child health and development

Dexamethasone, 143

Diabetes, 27, 72, 80, 98, 101, 113, 236, 263

Diethylstilbestrol, 114

DNA

damage and repair, 50

methylation, 113-114, 139

microarray technology, 111-112

sequencing technologies, 49-50

Dopamine

DRD2 gene, 73, 172, 264-265

DRD4 gene, 80

and eating behavior, 249

and nicotine addiction, 71

transporter, 73

Drug abuse, 39

Duke University, 290

Duncan Socioeconomic Index, 31, 32

Durkheim, Emile, 34

E

Earnings, 28

Eating behaviors (unhealthy)

access to energy-dense foods and, 240, 241, 242, 246, 250-251, 252, 269

animal research, 135

appetite and, 257, 258, 267, 268

and child health and development, 243-244, 247, 248

disinhibition trait, 246, 261, 267

epidemiology, 72

external cues and, 244, 246

fast-food consumption, 72, 241, 242, 250-251, 270-271

food advertising and, 252

gene-environment interaction, 72-73, 259-260

genetic influences, 72-73, 243, 257-262, 264-265, 267-268

health consequences, 72;

see also Obesity

heritability, 259-260, 267

hypothalamic response and, 135, 247

and mortality, 15

parent-child feeding dynamics and, 239, 243-245, 269, 271

portion size and, 247, 251, 269

reinforcing value of food and, 70, 75, 76, 172, 248-249, 264-265, 267

research opportunities, 267-268

restrictive feeding practices, 244-245, 271

satiation impairment and, 246-248, 267

satiety impairment and, 70, 73, 75, 135, 244, 248

self-regulation of intake, 244

smoking and, 172

social facilitation of, 72, 239, 242-243, 259

socioeconomic status and, 242

stress and, 301

style of eating, 135, 249-250

taste preferences and, 70, 75, 135, 172, 250, 257, 259, 268, 269

television viewing and, 252

time-extension mechanism and, 243

traits associated with obesity, 245-251

Eating Inventory, 261

EcoCyc, 124

Ecological model of health determinants, 18-19

EDN1 gene, 305

EDNRA gene, 305

Education and training of researchers conferences, 182

evaluation of programs, 184

fellowships, 182, 183-184, 185, 190, 233

K-12, 181-182, 183

private support, 187, 190

professional development, 184-186

recommendation, 9, 187, 233

short course approach, 185

social sciences, 183

T90 grant, 183-184

undergraduate, 185-186

Education quality, 27

Educational attainment

and health, 27-28, 39, 103

and smoking, 70

Edwards classification, 31

Embedded information. See Genomic information;

Metabonomics;

Proteomics

Emotional support, 34

Endothelin-1 gene, 76

Endotoxins, 118

Energy-dense foods, 240, 241, 242, 246, 250-251, 252, 269

Energy expenditure regulation and, 257

Engel, George, 281

Enkephalin, 301

Environmental Genome Project, 49, 64

Environmental genomics, 203

Epidemiologic approaches to interactions additive and superadditive models, 7, 8, 162, 163-164, 165-166, 168, 170, 173, 220, 313, 314, 315, 328, 334, 336

animal models, 330

biologic interaction, 311, 317, 322

biological plausibility restriction, 175, 177

Bonferroni correction, 174-175

case-control designs, 163, 168, 169, 170, 171, 174, 177, 329, 334, 335

case-only design, 49, 170, 177, 331-332

causal effect (causal contrast), 318, 319-322, 328, 330

causal model, 315-318

causal pies heuristic (causal pathways), 316-317, 319-320, 323, 331

causality in, 311, 312, 316, 319, 330-332

cohort designs, 163, 168, 169, 192-193, 329, 331-332, 334, 335

confidence intervals, 334-335

confidentiality issues, 171

confounding and bias, 62, 63, 65, 71, 168-169, 170, 171, 172, 174, 257, 319, 324, 330, 333, 335

counterfactual (potential outcomes) model, 8, 316-328, 330-335, 336

definitions of interactions, 7, 161-168, 176, 220, 312-316, 317

designs of studies, 57-58, 166-173, 176-177, 331-332

exposures, 171-172, 174-175, 311, 316, 319, 323-324

false positive test results, 175-176

family-based designs, 47, 49, 170-171, 332

framework for assessing interaction, 312-316

gene-environment interactions, 47, 49, 163, 166-173, 174, 311-312, 318, 329, 330-336

genetic context, 52, 62, 330-332, 333

genomic control methods, 169, 170

Henle-Koch principles, 310

human laboratory (intervention) research, 172

independent effect, 162, 165, 312

individual-level, 164-165

infectious disease models, 310

mathematical modeling, 327-330

measurement of environmental factors, 204, 333

measurement of interaction, 161-162

Mendelian randomization, 171-172

modeling innovations, 65

molecular techniques, 46

multiple comparisons, 175-176, 177, 334-335

multiplicative (log linear) or

supermultiplicative model, 7, 8, 162, 163-164, 168, 170, 173, 312-313, 332, 334, 336

for nonbinary outcome variables, 172-173

permutation testing, 174, 175

population stratification, 62, 63, 65, 71, 168-169, 170, 171, 172, 257, 335

power of, 8, 65, 166, 171, 172, 333-334

practical applications, 164, 328-330

preventive effects in, 328

primacy of genetic effect, 331

protective effects in, 168

psychologic interactions, 317, 328

recommendations, 7-8, 177

reproducibility of results, 48, 63, 175, 177, 193-194, 204, 257

risk factor framework, 162, 310-311, 335-336

sample size and power, 8, 65, 166, 169, 171, 172, 173-174, 177, 192, 193, 333-334

statistical methods and issues, 8, 161-164, 173-175, 177, 311, 312-313, 332

sufficient-component cause model, 8, 164-166

synergy (interaction) assessment, 165, 311, 315, 319, 322-330, 332-333

temporality, 170

uncertainties in, 71, 332-335

validation, 174

Epigenetic phenomena, 53, 64, 112, 113-114, 139

Epinephrine, 117, 118, 147, 286, 298, 301, 302, 304

ERCC2 gene, 50-51

Erythrocyte adhesion, 302-303

Ethical, legal, and social issues

civil liberties issues, 208-209

communicating research results, 203-205

community involvement in research protocols, 214-215

data security, 211-212, 220-221

disclosure of research results to participants, 212-213

discrimination and stigmatization, 202, 205, 207, 209-210

environmental regulation, 206-207

genetic association studies, 51

genetic screening, 209

health care issues, 202, 207

informed consent, 215, 216

insurance coverage, 202, 207

intellectual property rights, 203

intervention policies, 205-210, 220

lay oversight of protocols, 214-215

“moral hazard,” 206

new hypotheses arising from research, 214

privacy and confidentiality concerns, 171, 208, 211-212, 215-216

protection of research participants, 211

race/ethnicity as a proxy, 209

recommendations, 11-13, 210, 215-216

Eugenics movement, 205

Experimental allergic encephalomyelitis, 143-144

F

Familial aggregation studies, 47, 49, 170-171, 332

Familial dysautonomia, 101

Familial hypercholesterolemia, 45, 60-62, 203

Familial Mediterranean Fever, 101

Family Research Consortium III, 187, 190

Fast-food consumption, 72, 241, 242, 250-251, 270-271

Fetal

exposure to stressors, 139

hemoglobin, 284, 285, 289

nutrition, 39, 73, 113, 267

G

Gaucher disease, 101

Gel electrophoresis, 115

Gender. See Sex/gender

Gene-environment interactions

animal models, 76, 133, 134, 136, 137, 139-150

and biological characteristics, 64, 76

biological plausibility, 175, 177

cancer, 113

correlation model, 270-271

counterfactual model, 8, 316-328, 330-335, 336

CVD, 57-58, 75-76, 113, 137

depression and, 18, 80-82, 328-330

developmental consequences, 53, 113, 268, 271-272

eating behaviors and obesity, 72-73, 243, 257-262, 264-265, 267-268

epidemiologic approaches, 47, 49, 163, 166-173, 174, 311-312, 318, 329, 330-336

gene expression mechanisms and, 52-53, 113, 122

intermediate phenotypes as measures of, 74-82, 173

life-course perspective, 39, 47, 113-114

models of, 166-168

moderating, 76, 251, 262, 263-266, 269-270

molecular mechanisms, 116-122

for nonbinary outcome variables, 172-173

in obesity, 76, 113, 236, 237-238, 251, 260, 262-272

personality and, 35, 37, 78-79

physical inactivity, 74

and proteomics, 122

psychosocial work environment and health and, 37-38

racial/ethnic disparities in health, 99-101, 102, 104-105

research challenges and opportunities, 39, 40, 64, 266-272

responsivity to environmental factors, 50-52, 56, 139

social isolation, 36, 121, 141-142

statistical modeling, 65

study design and analysis, 57-58, 166-173, 176-177, 331-332

systems approach to modeling health, 123-126, 139

temperament and, 35, 37-38, 79, 140-141, 328

tobacco use, 50-51, 70-71

“toxic environments,” 269-270

Gene expression

databases, 124

defined, 287

developmental control of, 53, 54-55

DNA methylation and, 114

environmental influences, 52, 116-117, 122, 137

epigenetic phenomena, 53, 64, 112, 113-114, 139

fetal nutrition and, 73

and gene-environment interactions, 52-53, 113, 122

genetic variation in, 6, 110-114, 122

and globin, 54-55

heritability of, 111

in immune response, 288

life-course perspective, 5-6

mechanisms, 52-56

pharmacogenetics research, 60

post-transcriptional control, 53

serial analysis of, 111

sickle cell disease, 53-56, 284, 287

social environment and, 142

stress and, 118, 139, 142, 148, 287-288, 303, 305

transcriptomics technologies, 111-112

Gene-gene interactions, 46, 51-52, 56, 62, 236, 257

Gene Logic, 124

Gene Ontology Project, 112

Gene products, classification, 112

Genetic association studies.

See also Gene-environment interactions;

Gene-gene interactions

Bayesian networks, 288

BMI and fat mass, 255-257

DNA sequencing technologies, 49-50

eating behaviors, 261-262

ethical issues, 51

genome-wide approach, 111, 174

HaloChip assay, 111

population stratification in, 62, 63, 76, 168-169

race/ethnicity, 99

reproducibility, 177

sickle cell disease, 288, 299

SNP profiling, 49-50, 51-52, 58, 110

transcriptomic studies, 112

Genetic imprinting, 112, 113

Genetic linkage analysis

databases, 112

eating behaviors, 261-262

goal and principle, 47-48

sibling pair method, 48

statistical power, 48

whole-genome, 288

Genetic susceptibility.

See also Gene-environment interactions;

Gene-gene interactions

adverse drug reactions, 58-60

allelic heterogeneity, 45-46

aspects of health influenced by, 56-60

biases in studies, 49

cancer, 38 n.1, 45, 56, 149

clinical variability in diseases, 53-56

common disease, common variant hypothesis, 204

CVD, 45, 56, 57-58, 76

diabetes, 56

differential risk, 51

etiologic heterogeneity, 46

founder mutations, 60-61, 100

genetic association studies, 49-52, 255-257, 261;

see also Genotype and genotyping

hierarchy of causes, 311-312, 331

life-course perspective, 57, 254

linkage analysis, 47-48, 255, 261

linkage disequilibrium phenomenon, 62, 80, 175

locus heterogeneity, 46

mental illness, 56

molecular epidemiology techniques, 46

multifactorial models, 46, 48, 60, 65

nicotine addiction, 58, 71

obesity, 20, 72-73, 236, 248, 249, 253-262, 264-266

OMIM statistics, 45

overeating, 72-73, 243, 257, 259-262

pathway-driven study design, 50

penetrance of mutations, 45, 149, 312

polygenic models, 44-45, 46, 47, 60, 219

population-based measures, 47, 49, 63, 71

population distribution of variations, 60-62, 63

research approaches, 44-48

single-gene disorders, 44, 45-46, 47, 48, 53-56, 63-64, 73, 203-204, 219, 255, 257, 260

SNPs, 49-50, 51-52

therapeutic response to drugs, 56

to “toxic environments,” 241

Genome Science Education Program, 183

Genomic information

in biochemical systems, 114-116

comparative genomic hybridization assays, 112

epigenetic phenomena, 112, 113-114

and gene expression, 6, 110-114, 122

metabonomic technologies, 116

in proteomes, 111, 115

social and ethical implications, 203

transcriptomics, 111-112

Genotype and genotyping

array-based, 49, 52-53

interactions with environmental factors, 113-114

pharmacogenetic research, 59-60

moderator in gene-environment interaction, 269-270

multiplexing arrays, 49

SNP initiatives, 64

Geographic Information Systems, 269

German National Center for Environment and Health, 124

Glucocorticoids, 117, 118, 121, 137, 139, 145, 146, 298, 301

Glutamate, 303

GR gene, 299

Growth hormone, 301

GSTM1 gene, 51

GSTP1 gene, 51

GSTT1 gene, 51

Guyton, Arthur, 123

H

Health determinants

life course perspective, 5-6, 21, 22, 25-26, 219, 282

systems approach to modeling, 5-6, 17-19, 123-126

Health Insurance Portability and Accountability Act of 1996, Privacy Rule, 211

Health literacy, 28

Health outcomes. See Mortality;

Survival and functional recovery;

individual diseases

Health risk behaviors.

See also Eating behaviors;

Physical inactivity;

Tobacco use

definitions, 69-70

intermediate phenotypes, 70

outcome pathways, 68, 69

personality and, 70, 75, 77-79

social and cultural environment and, 30, 37, 71, 237-238

temperament and, 70, 75, 79-80

Hemochromatosis, 101

Hemoglobin gene expression, 53, 54-55

HER2 gene, 59

Heritability

of BMI and fat mass, 253-255

defined, 46-47.

See also Genetic susceptibility

of depression, 81

of eating behaviors, 259-260, 267

of gene expression, 111

narrow sense vs. broad sense, 253

High school dropouts, 28

High/Scope Perry Preschool Project, 28

Hispanics, 103.

See also Race/ethnicity

Histone acetylation, 114

HIV infection, 35, 77, 91-92

Home Observation for Measurement of the Environment (HOME) system, 268-269

Human DNA Polymorphism Discovery Program, 49

Human Genome Project, 3, 15, 64, 90, 109, 110, 123, 203

Human Obesity Gene Map, 255, 256

Hypertension, 27, 37, 94, 98, 102, 298, 299, 304

Hypospadias, 92

Hypothalamic-pituitary-adrenal (HPA) reactivity, 35, 81, 117, 118, 121, 135, 136, 139, 140, 143, 144, 145, 247, 297, 298-300, 301, 302, 303, 304

Hypothalamic-pituitary-ovarian axis, 301

I

Immune function

animal research, 134, 136-137, 138-141, 143-144

and CVD, 137

gene expression, 288

genetic determinants, 136

natural vs. specific immunity, 301, 302

obesity and, 72

sex/gender and, 93, 94

sickle cell disease and, 283, 287, 300-302

smoking and, 70

social environment and, 35, 134, 136-137, 138-139

stress and, 21, 117, 118, 119-120, 139-141, 145, 146-147, 148, 288, 297, 298-299, 300-302

Impulsive aggression, 18

Inclusion body myopathy, 101

Income

absolute vs. relative, 30

health associations, 29-31

measurement, 28-29

psychological and behavioral associations, 30

race/ethnicity and, 103

societal distribution, 31

tests of associations, 29-30

and weight gain, 241

Incyte, 124

Indians, Asian, 263

Infants

breastfeeding vs. bottle feeding and, 243-244

mortality, 27

secure attachments, 34

sucking rates and obesity risk, 249, 268

weight gain, 267

Inflammatory bowel disease, 101

Informational support, 34

Informax, 124

Informed consent, 215, 216

Infrastructure for transdisciplinary research

academic institutional structure and policies and, 10-11, 19, 181, 194-198

data, 19, 187-194, 220

education and training of researchers, 8-9, 19, 181-186, 193, 220

federal and industry research structures vs. academic, 197

IDR recommendations applied to, 10, 20, 186, 232-235

incentives and rewards, 10-11, 20, 193, 194-198, 220

MacArthur Network Model, 188-189

NIH support, 181, 182, 186-187, 194-198

P30 Core Grant and, 187

peer review, 10, 20, 195, 198-200

private support, 187, 188-189, 190

R01 Research Project Grant and, 186-187

recommendations, 8-11, 187, 199-200

support mechanisms, 186-187, 272

Institute for Public Health Genetics, 184

Institutional Review Boards, 210-211

Instrumental support, 34

Insulin-like growth factor, 74

Insulin resistance, 70, 72, 251

Interactions.

See also Gene-environment interactions;

Gene-gene interactions

definitions of, 7, 161-168, 176, 220, 312-316, 317

framework for assessing, 312-316

measurement of, 161-162

Interdisciplinary research (IDR)

academic institutional structure, 235

academic institutions’ policies, 233-234

defined, 3, 19

educators, 233

evaluation of programs, 235

funding organizations, 234

journal editors, 234

key conditions for effective programs, 194

MacArthur Network Model, 188-189

postdoctoral scholars, 190, 233

professional societies, 234

recommendations for facilitating, 10, 20, 186, 232-235

researchers and faculty members, 233

students, 232-233

team leaders, 234

Interferon γ, 301

INTERHEART Study, 78

Interleukin-1α, 143

Interleukin II, 288

Interleukin-6, 302

Intermediate phenotypes

and biological characteristics, 76

defined, 74-75

emotional/motivational states as, 80-82

measuring, 75-76

for obesity, 70, 73, 75, 78, 237

personality as, 75, 76, 77-79

for sickle cell disease, 288, 297

temperament as, 75, 76, 79-80

for tobacco use, 70, 75, 76

International HapMap Consortium, 64

International HapMap Project, 64, 190

Inuit of Greenland, 75-76

J

Job stress

and CVD, 57

effort-reward imbalance model, 37

job demand-control model, 37

K

Karolinska Institute Human Gene Bi-Allelic Sequences Database, 64

Kleinfelter Syndrome, 94

Kyoto Encyclopedia of Genes and Genomes, 112, 124

L

Laminin, 286

Leptin and leptin receptors, 73, 94, 134, 135

Life-course patterns of health

animal models, 139-140, 145

Barker hypothesis, 39

CVD, 57

determinants, 5-6, 21, 22, 25-26, 219, 282

early life experience, 39, 139-140

in gene-environment interactions, 39, 47, 113-114

in gene expression, 5-6

genetic susceptibility to disease, 57, 254

obesity, 74, 253, 266-267

physical inactivity and, 74

poverty, 4-5, 39

race/ethnicity and, 102-103

sex/gender and, 94

social-environment associations, 25-26, 27, 31, 32, 34, 39, 138

stress and, 118, 145, 300

in study design and analysis, 21, 22

Lipid metabolism, 119

Lung cancer, 50-51, 310

Lutheran blood group anitgens, 286

M

MacArthur Foundation, 187, 188

MacArthur Network Model, 188-189

Machine learning algorithms, 65, 112

Major histocompatibility complex, 138

Mass spectrometry, 116

Maternal

attachment, 36

education, 27

exposure to endocrine disrupting agents, 92

obesity, 267

separation, 35, 118, 121, 139

Matrix-assisted laser desorption ionization-time of flight mass, 115

MC4R (melanocortin-4 receptor) gene, 257, 258, 261

Media campaigns, 71

Mediation and mediating variables

in animal research, 137

in models of interactions, 167

of social environment, 147-148

of stress reactivity, 139, 147-148, 304

Melanoma, 38

Melatonin, 301

Metabolic Control Theory, 123

Metabolic syndrome, 236

Metabolism

gut flora and, 116

sex/gender and, 93-94

social stressors and, 145, 298

Metabonomics, 6, 112, 116, 124

Microarray Gene Expression Data Society, 112

Midlife health, 27

Migration, and genome selection, 109-110, 263

Minimum Information About a Microarray Experiment Guidelines, 112

Mitochondrial upcoupling proteins, 257

Modeling strategies

recommendations, 5-7

Moderation and moderating variables

animal research, 137

CVD risk, 76, 81

in gene-environment interactions, 76, 251, 262, 263-266, 269-270

of obesity, 76, 251, 262, 263-266

social environment, 262, 263

in stress response, 76, 285, 287-289, 290, 300

Monamine oxidase A deficiency, 208-209

Mortality

eating behavior and, 15

infant, 27

obesity and, 72

race/ethnicity, 98, 104

SES and, 27, 29, 104

smoking and, 70

social and behavioral factors and, 15, 27, 35

Moving to Opportunity study, 31

mRNA transcripts, 111-112, 118, 124, 146, 149, 287

Multidisciplinary research, defined, 3-4, 19

Multivariate statistical analysis, 137

Munich Information Center for Protein Sequences, 124

Myelosuppression, 59

Myocardial infarction, 35, 39, 70, 76, 78, 81, 82, 119

N

National Association of State Universities and Land Grant Colleges, 195

National Bioethics Advisory Commission, 213

National Cancer Institute

Breast and Prostate Cancer and Hormone-Related Cohort Consortium, 174

SNP database, 64

National Center for Biotechnology Information, dbSNP database, 64, 110

National Health Interview Surveys, 29

National Heart, Lung, and Blood Institute Programs in Genomic Applications, 49

National Human Genome Research Institute, 15-16, 50

National Institute of Environmental Health Sciences, 49

National Institute of General Medical Sciences, 16

National Institutes of Health (NIH), 97-98, 236

Certificates of Confidentiality, 211

Office of Behavioral and Social Sciences Research, 15-16

and transdisciplinary research, 181, 182, 186-187, 194-198

National Longitudinal Survey of Youth, 241

Supplement, 9, 190, 194

National Opinion Research Center Study, 31

National Research Service Act, 182

National Science Foundation, 181, 182

Native Americans, research protocols, 214-215

NEO-Personality Inventory, 77

Neophobia, 140

Network models, 65, 112

Network on Socioeconomic Status and Health, 188-189

Network theory, 204

Neurocognitive functioning, 283, 287, 293, 294-295, 297, 303

Neuroeconomics, 36

Neuroendocrine regulation, 35

Neuropeptide-Y, 257, 258

NGFI-A transcription factor, 139

Nickel, 114

Nicotine

addiction, 70, 79

and cardiovascular function, 70

cognitive and autonomic effects, 75

patch, 82

reward value, 70, 75, 76, 79

tolerance and deprivation, 70, 75

withdrawal and relapse, 79

Niemann-Pick disease, 101

NMB (Neuromedian-β) gene, 262

Norepinephrine, 147, 298, 301, 304

North Carolina Sickle Cell Center, 290

NOS1, NOS2, NOS3 genes, 305

NR3C1 gene, 137

Nuclear magnetic resonance spectroscopy, 116

O

Obesity.

See also Eating behaviors;

Physical inactivity

animal research, 73, 267

behavioral traits associated with, 245-251

BMI and fat mass, 69, 72, 73, 238, 253-255

breastfeeding vs. bottle feeding and, 243-244

children, 240-241, 244-245, 247, 248, 252, 261, 267

conceptual model of interactions, 237-238

critical growth periods for, 266-267

energy expenditure regulation and, 257

epidemiology, 72, 236

gene-environment interactions, 76, 113, 236, 237-238, 251, 260, 262-272

genetic influences, 20, 72-73, 236, 248, 249, 253-262, 264-266

health consequences, 72, 236

hypothalamic response and, 247

intermediate phenotypes, 70, 73, 75, 78, 237

life-course perspective, 74, 253, 266-267

macroenvironmental influences, 240-242, 268, 269-270

maternal, 267

microenvironmental influences, 242-245

moderating variables, 76, 251, 262, 263-266

personality and, 78

physical inactivity and, 74, 240, 251-253

race/ethnicity and, 155, 241, 244, 251, 252, 253, 261, 267

research opportunities, 266-272

restrictive feeding practices and, 244-245, 271

social environmental factors and, 20, 27, 72, 236-237, 238-245, 253-255, 263-266

socioeconomic status and, 239, 241-242, 264

“toxic environments,” 237, 239, 240-241, 251, 269-270

and underreporting of intakes, 247

Occupational status, 28

child health and, 39

and health, 31

measures of, 31-32

and weight gain, 241

Office of Management and Budget, 97

Online Mendelian Inheritance in Man (OMIM) statistics, 45

Osteoarthritis, 72

Ovarian cancer, 149

Oxytocin, 36, 145

P

Pain, 286-287, 289, 295-297, 299, 302

Pair bonding, 36

Panel Study of Income Dynamics, 29, 31

Parasitic infections, 137

Parent-child feeding dynamics, 239, 243-245, 269, 271

Path analysis, 123

Pattern recognition methods, 65, 112, 116

Peptidoglycan polysaccharide, 143

Persian Jews, 100, 101

Personality

and alcohol consumption, 78

“Big Five” model, 77-78

and CVD, 77-78

defined, 77

and depression, 78, 298

gene-environment interaction, 35, 37, 78-79

genetic factors, 78

and health risk behaviors, 70, 75, 77-79

as intermediate phenotype, 75, 76, 77-79

and obesity, 78

race/ethnicity and, 80

sex/gender and, 80

and social-environmental influences, 144-145

and stress response, 145, 298

and tobacco use, 78

Pew Charitable Trust, 182

Pharmacogenetics, 56, 58-60, 203

Phenylketonuria, 45, 167, 318

Physical activity

defined, 69

protective effects, 71, 73, 119

recommended, 69, 73

Physical inactivity

animal studies, 74

epidemiology, 73-74

gene-environment interactions, 74

genetic influences, 74

health consequences, 15, 73-74

life-course perspective, 74

nonexercise activity thermogenesis, 252-253, 268

and obesity, 74, 240, 251-253

research opportunities, 268

social/cultural environment and, 27, 72, 74, 240, 241, 242

television, video recorders and computers and, 240, 251-252

Pima Indians, 263-266

Pituitary function, 70

Polycystic kidney disease, 46

Population genetics, 60-62

Pound of Prevention Study, 251

Poverty.

See also Income;

Socioeconomic status/health associations

definitions, 30

gender and, 92-93

health associations, 25

life-course perspective, 4-5, 39

persistent vs. transient, 39

PPARγ gene, 257

Prader-Willi syndrome, 73, 255

Preschool education, 28

Privacy and confidentiality concerns, 171, 208, 211-212, 215-216

Pro-opiomelanocortin (POMC) peptides, 257, 258

Prolactin, 301

Promoter Database of Saccharomyces cerevisiae, 124

Prostate cancer, 174

Proteomics, 6, 60, 112, 114, 115, 122, 124

Psoriasis, 77

Psychological/psychiatric disorders and behaviors.

See also Depression

occupational status and, 31

personality and temperament and, 77

pharmacogenetics research, 59

SES of communities and, 18

social connectedness and, 35

Psychoneuroimmunology, 35

Psychosocial traits

animal models, 133, 135-136, 144

Psychosocial work environment/health associations.

See also Job stress

biases in, 37-38

gene-environment interactions, 37-38

evidence of, 25, 37-38

measures of, 31, 32, 37

occupational status and, 31, 32

reciprocal relationships, 37

Q

Quebec Family study, 262

Quebec Overfeeding Study, 269

R

Race/ethnicity

and ancestral origin, 98, 99

confounding issues, 98

context for research, 96-98, 99, 125-126, 219

definition, 97

gene-environment interactions, 99-101, 102, 104-105

and genetic variation, 38n.1, 61, 97, 99-104

health disparities and, 90-91, 98-104

life-course perspective, 102-103

and mortality, 98, 104

and personality, 80

and SES, 27, 103-104

SNP markers of phenotypic variation, 99-101

and social stressors, 39, 76

Racism and discrimination, 39

Random forest methods, 65

Renal function, 70, 305

Renin-angiotensin-aldosterone system, 299, 304

Reproductive dysfunction, 138, 118

Research. See Epidemiologic approach;

Infrastructure;

Interdisciplinary research;

Transdisciplinary interactions research

Rett syndrome, 113

Rheumatic diseases, 144

Risk behaviors. See Health risk behaviors;

specific behaviors

Risk prevention programs, 82

Rosetta, 124

S

Satiation, 246-248, 267

Satiety, 70, 73, 75, 135, 244, 248

Scale-free networks, 65

Science Education Partnership Awards, 182-183

Sedentary lifestyle. See Physical inactivity

Selective serotonin re-uptake inhibitors (SSRIs), 59

SELP gene, 288

Sephardi Jews, 100, 101

Serotonin

central nervous system responsivity, 18

pathways, 71

stress response, 298, 303

transporter (5HTTLPR) gene, 59, 76, 78, 80, 81-82, 145, 146, 147, 261, 305, 328-330

Sex/gender

animal research, 93

and body weight and fat stores, 93-94

context for interactions research, 94, 125-126, 219

and CVD, 92, 96

definitions, 91

and delivery of health care, 92

and energy metabolism, 93-94

and health, 90, 91-96

and heritability of food intake, 259

and immune response, 93, 94

independent dimensions in humans, 95

and life-course patterns of health, 94

and personality, 80

and poverty, 92-93

and social environment, 92-93

and stress, 93

synergistic effects of biology and gender relations, 91-92

variants, 95, 96

Sexual dimorphism, 94

Shotgun proteomic analysis, 115

Sickle cell disease

α-thalassemia, 285, 288, 289-290

ancestral origin and, 100

β-thalassemia, 54-55, 101, 284, 291, 292, 295, 296

cardiovascular and renal response, 286, 287, 304-305

clinical manifestations, 56, 286-287

definitions, 284

epistatic or modifier genes, 285, 287-289, 290, 300

erythrocyte adhesion to endothelial cells, 285, 286, 302-303

etiology, 283-284

and family functioning, 293

fetal hemoglobin, 284, 285, 289

gene expression, 45, 53-56, 284, 287

HPA activation and, 298-300

hydroxyurea treatment, 289

and immune response, 283, 287, 300-302

individual differences in severity, 282-283, 287-289

intermediate phenotype, 288, 297

maternal adjustment, 291-292

and neurocognitive functioning, 283, 287, 293, 294-295, 297, 303

pain, 286-287, 289, 295-297, 299, 302

pathogenesis, 284

pathophysiology, 55-56, 283, 285-286

psychological adjustment to, 287, 290-294, 295

resistance to malarial infection, 61, 100

severity, 54-55, 284-285, 286, 287, 289, 295

stress and, 20, 283, 287-288, 292, 297-305

and stroke, 286, 287, 288-289, 294, 305

sympathetic nervous system activation and, 298, 302

trait, 53-54, 284

Sickness behavior, 301

Silicon Genetics, 124

Simian immunodeficiency virus, 141

Single nucleotide polymorphisms (SNPs), 49-50, 51-52, 58, 62, 64, 99-101, 110, 168-169

SLC6A3 gene, 264-265

Sleep patterns, 301

Social and cultural environment.

See also Psychosocial work environment;

Social networks;

Social support;

Socioeconomic status

animal research, 36, 139-147

aspects of health influenced, 38-39, 57, 78

and biological processes, 36, 116-122

and cancer, 35, 38-39

context for interactions research, 5, 6-7, 21, 25-26, 125

cumulative effects, 39

and CVD, 31, 35, 57, 78, 119

defining, 21, 25-26, 238-239

and depression, 18, 31, 32, 35, 147

dynamic trajectories, 39

early life experience, 139-140

evidence of health associations, 26-38

and gene expression, 142

generational effects, 39

genetic selection of, 113-114

and health risk behaviors, 30, 37, 71, 237-238

and immune response, 35, 134, 136-137, 138-139

life-course, multilevel perspective, 25-26, 27, 31, 32, 34, 39, 138

macroenvironmental variables, 240-242, 268, 269-270

measures of, 204, 268-271

mediators of effects of, 147-148

microenvironmental variables, 242-245

moderating effects, 262, 263

and mortality, 15, 27, 35

natural policy experiments, 27-28

and obesity, 20, 27, 72, 236-237, 238-245, 253-255, 263-266

and personality, 144-145

population density, 138

research opportunities, 39, 268-269

and sedentary lifestyle, 27, 72, 74, 240, 241, 242

sex/gender and, 92-93

shared vs. unshared, 253-255, 267, 269

stressful, 20, 25, 30-31, 32, 39, 57, 78, 117-122, 138-139, 145, 146-147, 300, 312-313, 146-147

and temperament, 140-141

“toxic environments,” 237, 239, 240- 241, 251, 269-270

variables affecting health, 26, 240-245

Social attachment, 79

Social capital, 36-37

Social control, 37

Social isolation, 36, 121, 133, 138, 141-142

Social mobility, 32

Social networks/social supports and health

animal research, 141, 142, 147

bidirectional relationships, 35, 147

biological basis, 36

causality, 35-36

community-level, 36-37

confounding bias, 35

definitions and types, 34

and depression, 147

evidence of health effects, 25, 34-37

and health outcomes, 39

and immune function, 35

and incidence of disease, 39

measures of, 34-35

naturally occurring vs. strangers, 36

negative, 35

status and, 32, 302

temperament or personality and, 35

Social status.

See also Occupational status;

Socioeconomic status

animal research, 133, 144-146

personality and, 144

Social support. See Social networks

Socioeconomic status/health associations.

See also Social status

and cancer, 38-39

causal pathways, 27, 30, 32

causation, 27, 29, 32

and child health and development, 27, 29, 39

community-level, 18, 26, 30, 31, 241

confounding bias, 27

and eating behavior, 242

economic reserves, 31

education-related, 15, 25, 27-28

flow of resources, 31

income-related, 28-31

inherited ability and, 29

measures of, 26-27

moderating effects of, 76, 104, 264

and mortality, 27, 29, 104

and obesity, 239, 241-242, 264

occupational status-related, 31-33

psychological disorders and behaviors, 18, 30

and psychosocial stress, 30-31, 76

race/ethnicity and, 27, 103-104

relative deprivations, 30-31

research network, 188-189

reverse causation, 27, 29, 31-32

tests of, 29-30

variations in associations, 38-39

wealth, 31, 103-104

Spotfire, 124

Stanilas Family Study, 261

Statistical methods.

See also Epidemiologic approaches to interactions

Bonferroni correction, 174-175

confidence intervals, 334-335

gene expression profiles, 112

inferring causality, 137

Structural Equation Modeling, 123

Stress

acute, 148, 302

and alcoholism, 140, 145, 172

allostatic load, 118

animal research, 118, 120, 135, 137, 142-144, 145, 146-148

and autoimmune disease, 142-144

behavioral response, 139, 140

biochemical systems and processes, 117-122

and cancer, 140, 146, 148

and child development, 117, 118, 120-122, 139, 144, 147, 300

chronic, 118, 139-140, 148, 298, 300, 302, 303, 304

and CVD, 57, 78, 117, 118, 119, 298, 302, 304-305

defined, 117, 147-148, 297

deleterious coping behaviors, 32, 39

and depression, 81-82, 298, 301, 302, 313-314, 328-330

early life experiences, 145, 300

and eating behavior, 301

epigenetic programming, 139

and gene expression, 118, 139, 142, 148, 287-288, 303, 305

generational effects, 139

genetic differences in responsivity, 20, 142-144

health-promoting effects, 147-148

HPA axis activation, 297, 298-300, 301, 302, 303, 304

and immune function, 21, 117, 118, 119-120, 139-141, 145, 146-147, 148, 288, 297, 298-299, 300-302

as intermediate phenotype, 297

job-related, 25

life-course perspective, 118, 145, 300

and longevity, 118

magnitude of, 148

mediating variables, 139, 147-148, 304

moderators of, 76, 285, 287-289, 290, 300

nonsocial factors, 120

obesity and, 72

oxytocin and, 36, 145

and pain response, 301, 302

personality and, 145, 298

physiological responses, 72, 76, 81-82, 117-122, 147-148, 287-288

psychological response to, 21, 116-122, 302

race/ethnicity and, 39, 76

research opportunities, 39

SES and, 30-31, 76

sex/gender and, 93

and sickle cell disease, 20, 283, 287-288, 292, 297-305

social situations, 20, 25, 30-31, 32, 39, 57, 78, 117-122, 138-139, 145, 146-147, 300, 312-313

sympathetic nervous system activation, 297, 298, 301, 302

temperament and, 120, 140-141

Stroke, 35, 39, 82, 98, 119, 135, 286, 287, 288-289, 294, 305

Structural Equation Modeling, 123

Study design and analysis.

See also Epidemiologic approaches to interactions

life-course perspective, 21, 22

Suicide, 18, 81

Survival and functional recovery

cancer, 72, 73

obesity and, 72

personality and, 79

social environment and, 38, 39

Sympathetic nervous system reactivity, 35, 81, 118, 119, 144, 297, 298, 301, 302

Systems approach to interactions modeling, 123-124

biobehavioral model, 304

challenges in development and practice, 124-125

databases and systems analysis software, 124

gene-environment interactions, 123-126, 139

health determinants, 5-6, 17-19, 123-126

life-course perspective, 282

recommendations, 125-126

Systems biology, 123

System theory, 123

T

Tay-Sachs disease, 45, 101, 219

Television viewing

advertising, 252

and eating behavior, 252

and physical inactivity, 240, 251-252

Temperament

and ADHD, 80

animal research, 140-141

assessment, 79

and cancer, 140

defined, 77

gene-social environment interactions, 35, 37-38, 79, 140-141, 328

and health risk behaviors, 70, 75, 79-80

and immune function, 120

as intermediate phenotype, 75, 76, 79-80

and social and cultural environment, 140-141

and stress response, 120, 140-141

and tobacco use, 77, 79, 80

traits, 79

Temperament and Character Inventory, 79

Testicular cancer, 96

TGFBR2, TGFBR3 genes, 288

Thiocyanate, 70

Thiopurine methyltransferase deficiency, 59

Thiopurines, 59

$1,000 Genome Project, 50

Thyroid function, 70

TNFα gene, 76

Tobacco use

advertising and, 79

bupropion treatment, 172

cessation, 82, 172

and CVD, 57, 58, 70

definition of smoking, 69

depression and, 71

epidemiology, 70

gene-environment interactions, 50-51, 70-71

genetic susceptibility to nicotine addiction, 58, 70, 71

health consequences, 15, 57, 58, 70

intermediate phenotypes, 70, 75, 76

life-course perspective, 74

and lung cancer, 70, 310

nicotine addiction, 69, 70

personality and, 78

risk factors for initiation, 71

smoking persistence, 69

social and cultural environment and, 27, 30, 31, 32, 37, 70-71, 79

and social policy, 207

temperament and, 77, 79, 80

Transcription Factors Database, 124

Transcriptomics, 6, 111-112, 124

Transdisciplinary interactions research.

See also Epidemiologic approaches to interactions;

Infrastructure for transdisciplinary research

barriers to, 19-20

behavioral and psychological variables, 4, 5, 125

biological signatures, 126

defined, 4, 19, 220

diversity of groups and settings, 126, 220

funding, 272

genetic factors, 4, 125

hiring, promotion, and tenure policies and, 195-196

life-course perspective, 4-5, 94, 125

minority subjects in, 97-98

physiological measures and pathways, 4, 22, 125

race/ethnicity context, 4, 96-98, 125-126

recommendations, 3-5, 125-126

sex/gender context, 4, 94, 125-126, 219

social variables, 4, 21, 25-26, 125

systems modeling approach, 3, 5-6, 123-124, 126

team approach, 186-187, 195-196

Trust, 36

Tumor necrosis factor-alpha, 147

Tumor suppressor gene, 149

Turner’s syndrome, 91, 95

Twin studies, 47, 71, 81, 254, 255, 258, 264, 266-267, 269-270, 299

U

UCP1, UCP2, UCP3 genes, 257

Ulcerative colitis, 77, 101

University of Washington, Seattle, 184

U.S. Department of Health and Human Services, 211

V

Vasopressin 1a receptor gene transfer, 142

W

What Is There, 124

Wisconsin Longitudinal Survey, 32

Work environment. See Psychosocial work environment

World Health Organization, 69, 72

Wright, Sewall, 123

X

Xenobiotics, 114

XRCCI gene, 50-51