Index
A
ACE gene, 98
Activities of daily living (ADLs), 67, 163, 168, 174, 339
Activities of Daily Vision Scale, 168
Adams, Julian, 80
Addictive behaviors, 45, 50, 78n.11, 86, 102, 116
Adematous colon polyps, 237
Administrative data linkages, 3, 13, 236, 251, 252, 256, 258, 271, 330
Adoption studies
bias in, 44
with biological offspring of adoptive parents, 119
designs, 118–119
of familiality, 118–119, 234–235
of genetic factors, 43–44
of mental illness, 234–235
representativeness of sample, 119
Adrenocorticotropic hormone (ACTH), 26
Advanced activities of daily living (AADLs), 163, 168
Advanced intercross, 222
Advocacy and support groups, 320
Affected sib-pair linkage analysis, 121
Affinity chromatography, 29
African Americans, 94, 102, 143, 282.
See also Race/ethnicity
Age/aging.
See also Biomarkers of aging;
Life span;
Longevity;
Mortality;
Mouse models of aging
actuarial quantification approach, 183– 184
and antioxidant levels, 24
biological, indices of, 184–185, 231–232
caloric restriction and, 182, 187–188, 204, 206–207, 232
and disease processes, 231, 232
“elite” vs. “successful,” 144
energy resource allocation and, 232–233
environmental factors in, 182, 187–188, 204, 206–207, 232
and gene expression changes, 133, 134– 138, 182, 206–207
and genetics of disease risk, 73–74, 93, 97–98, 133, 232–233
homocysteine and, 21
intercellular signaling systems and, 161
interindividual differences in, 184–185
interpopulation differences in rate, 194
major surveys on, 2
multiple-clocks model, 181–182
and onset of disease, 48, 76, 94, 140, 141, 143, 234, 238, 263, 314
paternal, and mutations in offspring, 139
and physiological function, 143–144, 159–176, 182
sample collection considerations, 243, 246, 265, 267, 297
single-clock model, 182–183
and societal functioning, 162–163
and stereotypic expectations, 162–163
and telomere shortening, 232
Aging Research Center, 53
Alcohol/alcoholism, 45, 50, 78n.11, 86, 218, 224, 282
Allele-sharing methods for QTL mapping, 121–122
Alleles
APOE, 50, 52, 73, 74, 78, 83, 88, 90, 93– 94, 102, 143, 225, 340
common, 71
geographic distribution of, 72, 141, 148, 238, 239
HPC, 241
SNPs, 67
Alliance of Genetic Support Groups, 320
Allostatic load, 3, 25–26, 334–335, 339
Alpha secretases, 141
Alzheimer’s disease
APOE genes and, 50, 71, 73, 74, 90, 91– 92, 93, 94, 101, 143, 145, 241, 263, 264, 314, 340
complex-trait models, 114
data collection issues, 236, 298
early-onset, 140
environmental considerations, 93, 94
gender differences, 93
late-onset, 263
race/ethnicity and, 94, 142–143
twin studies, 45
American Academy of Pediatrics, 297
American College of Medical Genetics, 297
American College of Pathology, 148
American Society of Human Genetics, 293, 297, 311
Amyloidosis, 197
Anemia, 271
Animal model research
advanced intercross groups, 222
backcross groups, 223
of biomarkers of aging, 187–192, 193
comparison with human studies, 188
of diabetes, 222
dogs, 204–205
environmental variables in, 215–217, 223
fruit flies, 184, 215, 222, 224
gene mapping, 222
genetic variables in, 217–223
genetically heterogeneous stocks, 219– 223
genotype constraint, 217–219
genotypic selective breeding, 225
IL-6-stress relationship, 22
inbred strains, 217–219, 221, 222, 223
manipulation of genes in, 223–225
See also Mouse models of aging
microarray analyses, 138
model systems, 214–223
nematode worms, 182, 205, 217, 222
phenotypic selective breeding, 224–225
quantitative genetic model, 113, 226
rationale for, 214
recombinant strains, 223
relevance for human populations, 213– 227
representativeness of strain, 218, 219– 220
Rhesus monkeys, 200
species choice, 214–215
statistical power, 219
transgenic and knock-out preparations, 225
validity for humans, 225–227
wild-trapped animals, 220
yeast, 222
Antagonistic pleiotropy, 97, 340, 342
Anthropometric measurements, 54, 254, 271
Antibody production, 201
Anticlotting agents, 23
Antisocial and criminal behavior, 87
APOB gene, 98
Apolipoprotein E (APOE) genes, 150, 331
and Alzheimer’s disease, 50, 71, 73, 74, 90, 91–92, 93, 94, 101, 143, 145, 241, 263, 264, 314, 340
animal model, 225
BRCA genes compared, 91–94
and cardiovascular disease, 50, 73, 74, 78–79, 83, 91, 92–93, 94, 96, 143, 145, 264, 340
case-control studies, 75
and cognitive function, 18, 50
cohort studies, 88
defined, 340
and demographic modeling, 18, 73–74, 90, 91–94, 99
and diabetes, 50
e2 allele, 143
e3 allele, 225
e4 allele, 50, 52, 73, 74, 78, 83, 88, 90, 93– 94, 102, 143, 263, 265, 340
environmental interactions, 50, 94
genotype/genotyping, 30, 50, 60, 73, 74– 75, 92, 145, 254
and head trauma recovery, 52
and mortality risk, 74–75, 78–79, 83, 88, 91–92, 93, 102
population frequencies, 92–93
polymorphisms and rare alleles, 73, 91, 92–93
race/ethnicity and 18, 79, 85, 92–93, 102, 143
Arteriosclerosis, 142
See also Osteoarthritis;
Rheumatoid arthritis
Assets and Dynamics Among the Oldest Old (AHEAD), 251
biological samples and, 236
with candidate genes, 69–70, 86, 97, 123– 124, 240
case-control design, 87, 123, 133, 142– 143, 239–240
of dementia, 142–143
elements of, 214
environment-disease, 240
founder effects, 123
genetic drift and, 123
of inheritance patterns, 69–70, 78
linkage methods integrated with, 121, 125
population-based, 239–241
of psychiatric disorders, 86
race/ethnicity and, 70, 123, 142–143
spurious associations in, 123–124
with tightly linked markers to functional genes, 123–124
transmission/disequilibrium tests, 124– 125
Assortive mating, 95, 117, 118, 340
Atherosclerosis, 24, 50, 162, 233
Atherosclerosis Risk in Communities study, 27
Attention/attentiveness, 166
Attrition, biological sample collection and, 29, 30, 55–56, 59, 242–243, 270
Autism, 45
Autoimmune diseases, 260
Autopsies
of accident victims, 150
costs, 149
genetic analysis of samples, 150
hospital, 150
population-based studies of geriatric populations, 4–5, 134, 150
rates, 148–149
sources of materials from, 149–150
B
Baby-boom cohorts, 252
Backcross groups, 223
Bacterial artificial chromosomes (BACs), 139, 340
Balance, 18
Baltimore Longitudinal Study of Aging, 162
Bangladesh, 271
Base sequence, 340
Basic activities of daily living (BADLs), 168, 258
Behavioral genetics
in addictions, 45, 50, 78n.11, 86, 102, 116
association studies, 86
community-based studies, 241–242
and demographic analysis, 76, 78n.11, 85–87, 100
generalizability of findings, 100
psychiatric disorders, 86
research opportunities, 330–331
Beta amyloid precursor protein, 140–141, 150
Beta secretases, 141
Between-population differences, in gene—environment interactions, 85, 90, 95
Bias
in adoption studies, 44
in case-control studies, 142, 240
environment-disease association studies, 237–238
in genetic epidemiology, 235
in linear regression, 77–78
in logistic regression, 78
population stratification, 239
in risk assessment, 255
sampling, 86, 98, 111, 150, 239, 253
type I errors, 237
Biodemography, 340
Bioindicators.
See also Biomarkers
advantages in social surveys, 4–6, 254–265
appropriateness, 9
blood samples as, 171–172, 254
of cardiovascular system, 18, 19, 20, 21, 22
changes over time, 256
cholesterol as, 15, 19, 22, 25, 254
cognitive function, 21, 22, 23, 24, 25
collaborative research opportunities, 272
defined, 340
in demographic approach, 14–16, 94
environment-health linkages from, 259– 263
fertility, 15
gene expression data and, 207, 208
height and weight as, 329–330
historical context, 329
for inclusion in household surveys, 17– 26, 31, 254
liabilities in social surveys, 265–266
lung function, 19, 20, 24, 28, 54, 161–162, 174
of metabolic processes, 19–21, 161
renal function, 19, 20, 24, 159, 161, 170, 172
and representativeness of nonclinical data, 254–256
self-report calibration with, 256–259
SNS activity, 19, 20, 23, 25, 29
symptoms, 15
value of, 330–336
Biological determinism, 320
Biological pathways, 16
Biological specimens.
See also Blood samples;
Collection of biological specimens;
DNA samples/sampling;
Pathology samples;
Repository specimens;
Urine samples and association studies, 236
from autopsies, 149–150
genetic specimen sources, 149–150, 245– 246, 276
for hypothesis testing, 208
transport and storage, 244–245, 268
Biomarkers.
See also Bioindicators of coagulation processes, 20, 21–22, 161
in epidemiologic studies, 17
of inflammation processes, 19, 20, 21–22, 25
of neuronal cells, 137
Biomarkers of aging, 17
animal model research, 187–192, 193
criteria for, 185–186
gender and, 188–189, 191–192, 193
hormonal/reproductive history, 191–192
indices of biological age and, 184–185, 231–232
life expectancy correlated with, 186
molecular, 134
mouse studies of, 187–192, 193
physiological reserve and, 186
secondary evaluation criteria, 187
T-cell subsets, 187–192, 193, 200–201, 206
validation of, 185–186
Biomedical assessments, 28
Biometric models, 44
Blood pressure.
See also Hypertension alcohol and, 50
BMI and, 96
diurnal fluctuations, 161
measurement, 19, 20, 25, 28, 161, 290
race/ethnicity and, 256
Blood samples, 19
collection, 29–30, 55, 57, 58, 243, 254, 271, 279
indicators of function, 171–172
interpretation considerations, 172
Body mass index, 15
and blood pressure, 96
and cardiovascular disease, 96
measurement of, 20
Bone density, 74, 96–97, 189, 201, 237
Bone fractures, 23, 89, 96–97, 237
Bone marrow function, 161
Bone matrix turnover, 203
Boston University, 312
Brain
gene expression in, 85–86, 137
GFAP levels, 203
BRCA genes
APOE gene compared, 91–94
defined, 341
as demogenes, 91–94
and mortality risk, 91–92
polymorphisms and rare alleles, 84, 92– 93
Breast cancer, 46, 74, 84, 91–94, 101, 237, 294, 319, 320, 341
Brown, Pat, 135
C
C-reactive protein (CRP), 20, 21, 22, 25, 30
Caloric restriction
and gene expression, 206–207
Cancer.
See also individual sites cultural practices and, 84
heritability of, 68, 90–91, 139, 142
and longevity in mice, 196–197, 198
repository-sample issues, 293, 294
self-reports of, 17
stress and, 260
telomere shortening and, 232
tumor suppressor genes, 138–139, 142
Cancer Genetic Studies Consortium (CGSC), 320
Candidate genes.
See also Demogenes association studies with, 69–70, 86, 97, 123–124, 240
confirmatory role of social surveys, 321
defined, 341
Human Genome Project and, 72
for longevity, 87–88, 97–98, 141–142, 182, 203, 342, 344
for psychiatric disorders, 86
Capron, Alexander, 294
CARDIA, 27
Cardiac arrhythmias, 161
Cardiovascular disease.
See also Heart disease;
individual disorders and diseases
allostatic load and, 25
APOE gene and, 50, 73, 74, 78–79, 83, 91, 92–93, 94, 96, 143, 145, 264, 340
bioindicators of, 18, 21, 23, 24
BMI and, 96
cholesterol and, 96
cortisol and, 23
environmental influences, 116
gender differences in outcomes, 93
gene-environment interactions, 12, 94, 233
genetic factors, 48, 50, 73, 74, 78–79, 83, 91, 92–93, 94, 96, 143, 145, 340
Cardiovascular Health Study, 27
Cardiovascular system
bioindicators of health, 18, 19, 20, 21, 22
functional assessment, 161, 162
and self-efficacy and control, 23
Case-control studies
of APOE mortality risk, 75
demographic analyses used with, 77
of environment-health interactions, 240
of gene-disease associations, 87, 123, 133, 142–143, 239–240
of gene-environment interactions, 241
limitations of, 74, 142–143, 240
point estimates, 77
for qualitative traits, 123
Catecholamines, 23, 26, 207, 267
Causation, 90n.21
Cause-of-death associations, 189, 196–200, 238
Center for Epidemiological Studies Depression Scale, 261
Centers for Disease Control, 277, 286, 297
Cerebrovascular disease, 21, 166
Challenge, and health, 23, 260–262
Chemtech, 136
Children
genetic testing of, 296–298, 314
Chinese populations, 27, 92, 95n.22, 251, 253–256, 261, 264, 271
Cholesterol, serum
as bioindicator of health status, 15, 19, 22, 25, 254
and cardiovascular disease, 96
components, 19–20
and functional status, 22
measurement of, 20, 29, 254, 288, 290
race/ethnicity and, 85
synthesis errors, 49
Chromosomes, human
(4), 64
(6), 87
(12), 49
(19), 71
Chromosomes, mouse
(6), 195
(9), 195
Chronic fatigue, 263
Chronic obstructive pulmonary disease, 46
Clinical Laboratory Improvement Amendments, 289
Clinical samples and tests, 27, 150–152, 160, 161, 170, 173, 243, 289
Clones/cloning
positional, 64, 70, 71, 194, 345
Cluster analysis algorithms, 135
Coagulation processes, 19, 20, 21–22, 161
Cognate DNA sequences, 139
Cognate genes, 135
Cognitive function
assessment, 3, 28, 54–55, 144, 167, 258
bioindicators of, 21, 22, 23, 24, 25
dimensions of, 166
heritability of, 47, 86, 87, 234
and informed consent, 270, 298
integrative, 167
lung function and, 24
and physical function, 163
population studies, 11, 150, 237, 258
and self-reports, 258
stress and, 260
Cohort studies.
See also Population-based research and surveys;
individual studies
of APOE genes, 88
collection of biological materials in, 54– 55
disease risk trends, 74
of gene-disease relationships, 239–240
of gene-environment interactions, 50–51, 54–55, 238, 240
in genetic epidemiology, 88–89, 235
temporal associations in, 238
COLIA genes, 70
Collection of biological specimens.
See also Biological specimens;
Measurement of function;
Sampling strategies
age considerations, 243, 246, 265, 267
benefit to study participants, 269, 282
clinic-based protocols, 27, 160, 173, 243, 254
in cohort studies, 54–55
and compromise of research objectives, 265, 268–269, 341
costs, 6–7, 56, 59, 207, 251, 254, 265–266, 267–268, 271
cytological/cellular samples, 148, 161, 172–173, 245
Danish 1995–1999 experience, 3, 53–55, 56
in family studies, 208
for gene mapping, 208
for genetic epidemiology, 42–43, 51–53
informed consent for, 270, 279–280
in-home, 6, 243, 254, 258, 267
logistical issues, 26, 243–244, 254, 267– 268
pilot studies of, 28–29, 243, 253, 264, 266
in population surveys, 16–17, 26–30, 53– 60, 207, 236, 242–246, 263, 265–269
quality control, 60, 244, 251, 268
from repositories, 246
respondent burden, 6, 266–267, 297–298
staff training for, 7, 243, 268
and study participation rate, 6, 29, 30, 55–56, 59, 242–243, 251, 266
Collection of data
anthropometric measurements, 54, 254, 271
family structure and disease data, 236
in household surveys, 12–13, 16–17, 53– 60, 161–162, 236
proxy interviews, 12, 59, 173, 175, 236, 252, 253, 256, 270
self-reports, 12, 16–17, 26, 30, 174, 175– 176, 256–259, 262
College of American Pathologists Ad Hoc Committee on Stored Tissue, 286, 294, 295
Collins, Francis, 320
Colon/colorectal cancers, 115, 146–148, 237
Communication of research results, 265, 268–269, 288–290, 297, 341
Community-based behavioral studies, 241– 242
Comparison disparate studies, 74–75
Complex quantitative traits
defined, 67
in founder populations, 239
Confidentiality issues, 255
Certificate of Confidentiality, 309
importance of, 270–271
informed-consent protections, 280–281, 291, 292–293, 297
Congenital hypothyroidism, 151
Congestive heart failure, 159, 170, 197
Consanguineous matings/marriages, 140
Consumer rights movement, 278
Contamination effects, 265, 268–269, 341
Controls.
See also Case-control studies in demographic studies, 77–78
in family studies, 111, 124–125, 126
in nested case-control studies, 51
in population studies, 239, 263
racial/ethnic considerations, 51
Coronary artery disease, 95, 96, 100, 170, 237
Coronary heart disease, 22
Cortisol, 20, 22–23, 25, 29, 172, 254, 267
Cost considerations
in autopsies, 149
in biological specimen collection, 56, 59, 207, 251, 265–266, 267–268, 271
laboratory assays, 136, 137, 267
Covariation, among relatives in family
Cox regression analysis, 51, 88
Creatinine clearance, 20, 24, 29
Cross-cultural studies, 255–256
Cross-national comparisons, 76
Cross-sectional analysis, 238, 255
Crossover effect, 201, 221, 341
Crow, James, 139
Cryopreservation of surgical tissues, 145, 146
Cultural considerations, in genetic research, 282–283, 317–319
Cultural practices, and cancer, 84
Cultural transmission effects, 113, 117, 118, 140
Cytological/cellular samples and tests
collection of, 148, 161, 172–173, 245
gene expression screening by cell type, 206–207
D
Danish Center for Demographic Research, 53
Danish 1905-Cohort Study, 53, 54–56, 59
Danish Twin Registry, 54
Death certificate data, 134, 148, 150
Dehydroepiandrosterone sulfate (DHEAS), 20, 22, 23, 25, 29, 254, 256
Delayed paragraph recall test, 144
Dementias, 137.
See also Alzheimer’s disease
association studies of, 142–143, 239
background rates, 142
and language function, 166
and physical functioning, 163
population studies of, 258
Demogenes
APOE as, 18, 73–74, 90, 91–94, 99
for body mass index, 95
BRCA as, 91–94
for coronary artery disease, 96
evidence from genetic epidemiology, 94–99
gene-environment interactions, 90, 94, 95
for hypertension, 95–96
identification of, 89–94
for longevity, 97–98
for osteoporosis, 96–97
prospects for, 98–99
Demographic approaches/models
of age pattern of mortality, 81–83
of APOE gene, 18, 73–74, 90, 91–94
behavioral genetics in, 76, 78n.11, 85–87, 100
bioindicators in, 7, 14–16, 94
case-control data combined with, 77
common mechanisms, 9
comparing disparate studies, 74–75
complex quantitative traits and, 72–75, 239
controlling for genotype in, 77–78
of fertility, 11
of gene-environment interactions, 90, 94, 95
genetic epidemiologic surveys and, 88– 89, 94–100, 101–102, 242
genetic marker distributions, 238–239
in genetic research, 65, 66, 72–75, 100–101
health outcome models, 13–14, 76–81, 84–85
of individual differences in outcomes, 76–81
and informed consent, 279
longevity genes and, 76, 87–88
of major genes for common diseases, 73–74, 89, 242
of population differences in outcomes, 84–85
time considerations, 101
variables of interest, 67
Diabetes mellitus
animal models, 222
APOE gene and, 50
race/ethnicity and, 16, 21, 319
TDT for, 124
Dimensionality reduction, 6, 335
Disease and disease processes.
See also Health outcomes;
individual diseases and disorders
age-at-onset considerations, 48, 76, 94, 140, 141, 143, 234, 238
age-related rates of change in, 231
aging distinguished from, 232
cohort studies of risk trends, 74
dimensions of, 231
family studies of, 234–235, 236
gene-environment interactions, 12, 44, 49, 79, 84, 94, 95, 114–115, 146, 233, 263
genes for, 64, 65, 73–74, 79, 97
genetic variance in, 49–50
misclassification of conditions, 234
registries, 239
Divorce, 48
Dizygotic (fraternal) twins, 44, 54, 68, 117, 234
DNA
adducts, 244
cognate, 139
defined, 341
genomic, 139
junk, 342
recombinant, 346
repair, 232
variants, 72
DNA samples/sampling
age considerations, 246
alternative sources, 245–246
cheek brushes, 54, 57–59, 173, 208, 243, 263, 265
finger prick, 54, 56–57, 58, 173, 208
for gene mapping, 208
in genetic epidemiology, 43
in-home collection, 243
mouth lavage, 56
participation rates, 59
quality control, 60
size of, 208
urine, 56
Dogs, height-life span nexus, 204–205
Dominant gain-of-function mutations, 140
E
Economic models of health, 10, 14, 260
Economic returns to education, 68
Educational attainment, and outcomes, 333
Effect modifiers, genes as, 78–79, 139
Effect size, 18
Egypt, 271
Empirical results, 10
Endocrine function, 23, 161, 171, 194
Endometriosis, 197
Endorphins, 207
Environment-health interactions.
See also Gene-environment interactions
and age-related physiological change and disease, 182, 187–188, 204, 206– 207, 232
in Alzheimer’s disease, 93, 94
in animal model research, 215–217, 223
bioindicators of, 259–263
biological factors, 5
candidate agents, 125
and cardiovascular disease, 116
case-control studies, 240
chemical factors, 5
compromise approach, 116
in family studies, 117
and genetic variance, 48
major qualitative exposure to risk factors, 112, 115
measurable effects, 3–4, 116–117, 126
migration studies, 235
monitoring systems, 3–4
physical factors, 5
polyenvironmental influences, 115–116
in quantitative genetic models, 115–117, 125, 127
shared environmental effects, 117, 118
Eosin, 144
Epidemiological models, 10–11, 12–13.
See also Genetic epidemiology
biomarkers in, 17
Epigenetic changes, 146–147, 341
Epinephrine, 20, 23, 25, 29, 254
Epistatic effects, 114, 222, 341
Equal environment assumption, 45, 117
Established Populations for Epidemiologic
Studies of the Elderly (EPESE), 27, 89, 256, 341
Estrogen receptor gene, 146–147
See also Confidentiality issues;
Informed consent;
Privacy of genetic information
communication of research results, 288– 290
in genetic marker research, 264–265
in genetic testing, 281–283, 291–292, 297, 317–319
group-related harms, 282–283, 304, 317– 319
HGP budget for, 304
historical reports, 304–305
ownership of repository specimens, 245, 295, 311–315
paternity misattributions, 236, 292, 307, 316
psychological risks, 315–317
research agenda on, 7, 322–323
responding to change in genetic research, 321
in social surveys, 255, 264–265
Ethical, Legal and Social Implications Program, 322–323
Ethnohistorical distance between populations, and cancer mortality, 84
Eugenics, 281
Evolutionary theory, 110
Executive function, 167
Extraversion, 47
Eye tumor retinoblastoma, 239
F
F1 generation, 220–221, 222, 223, 342
Familiality
adoption studies, 118–119, 234–235
information sources, 236
nuclear family studies, 118
in twins reared apart, 68, 119
twin studies, 117–118
in unrelated children, 235
Family studies.
See also Adoption studies;
Twin studies
biological samples, 208
covariation among relatives in, 113, 115, 118
cultural transmission model in, 118
design of, 111–112
of diseases and disorders, 234–235, 236
environmental considerations, 117
gene-environment interactions, 42, 118
in genetic epidemiology, 68
of genetic markers, 240–241
generalizability and representativeness of, 118
of heritability of traits, 68, 120, 254
limitations of, 111–112, 118, 124–125, 236
parent-offspring pairs, 119, 125, 208
Fatty acid oxidation, 151
See also Reproduction
Fibroblast growth patterns, 203
Fibromyalgia, 263
Fibrosarcoma, 189, 196, 197, 198
“Fight or flight” responses, 23
Founder effects/populations, 85, 90, 93, 123, 141, 239, 342
Frailty, heterogeneity in, 75
Framingham Genomic Medicine, Inc. (FGM), 312
Framingham Heart Study, 10, 27, 89, 312
Framingham Offspring Study, 89
Free radicals, 24
Fruit flies, 184, 215, 222, 224
Function.
See also Physiological functions
assessment of, 158;
see also Measurement of function
integrated, 3, 162, 168–169, 174, 175
levels of, 160–163
types of, 163–169
Functional reserve, 170, 171, 186
G
Gamete, 342
Gamma secretases, 141
Gender/sex
and addictive behavior, 45
and Alzheimer’s disease, 93
and antioxidant levels, 24
and biomarkers of aging, 188–189, 191–192, 193
and cardiovascular disease outcomes, 93
and fertility, 47
and health behavior, 254
and heritability of traits, 45, 47
and intelligence, 87
and life expectancy, 15
See also Microarray analysis
Gene-environment interactions.
See also Genetic epidemiology
aging-related, 5
and between-population differences, 85, 90, 95
challenges in studies, 42, 51–53, 87, 114
cohort studies, 50–51, 54–55, 238
community-based behavioral studies, 241–242
and demographic studies, 90, 94, 95
design of studies, 50–51, 79, 150
in diseases and disorders, 12, 44, 49, 79, 84, 94, 95, 114–115, 146, 233, 263
height as expression of, 329–330
and longevity, 98
in mental illness/disorders, 44, 86, 241– 242
multiple comparison problem, 52–53, 70
sample size considerations, 237
and segregation analysis, 69
toxicant metabolism, 241
twin studies, 44–45
Gene expression
aging-related changes in, 133, 134–138, 182, 206–207
and bioindicators of clinical states, 207, 208
caloric restriction and, 206–207
epigenetic changes in, 146–147, 341
microarray methodologies, 120, 133, 135–139, 145, 150, 344
in peripheral blood samples, 145
protein modulation of, 146
quantitative analysis of, 139
screening by cell type, 206–207
suppression, 341
technology, 127
transcription factors and, 134
Gene-gene interactions, 85, 87, 225
Gene mapping
in affected sib-pairs, 121
in animal models, 222
biological sample collection for, 208
defined, 342
linkage analysis, 120–121
of Mendelian major factors for disease loci, 120
multipoint, 121
pedigree data and, 120–121
positional cloning, 64, 70, 71, 194, 345
QTL studies, 86, 121–122, 125, 194–195, 201, 203, 222
in quantitative genetic model, 113, 119
sib-pair allele-sharing methods, 121–122
tandem repeats, 346
Gene promoters, 146
Generalizability of findings
in behavioral genetics, 100
in family studies, 118
Genes.
See also Apolipoprotein E;
Demogenes;
Major genes ACE, 98
and age patterns of mortality, 81–83
for Alzheimer’s disease, 50, 71, 73, 74, 90, 91–92, 93, 94, 101, 143, 145, 340
APOB, 98
asthma susceptibility, 239
and behavior, 85–87
BRCA, 84, 91–94, 101, 294, 319, 341
cognate, 135
COLIA, 70
for common diseases, 73–74
as controls, 77–78
defined, 342
demographic models for, 73–74, 89, 242
as effect modifiers, 78–79, 139
estrogen receptor, 146–147
FAP, 294
functional, 123
and heterogeneity in survival analysis, 80–81
for Huntington’s chorea, 64, 65
manipulation in animal models, 223–225
for obesity, 79
for osteoporosis, 97
for phenylketonuria, 69n.4
pleiotropic effects of, 97, 200, 205, 331, 345
for sickle-cell anemia, 65
tumor suppressor, 138–139, 142
for type I collagen, 70
Genetic analysis.
See also Linkage analysis of autopsy samples, 150
risks associated with repository tissues, 281–283
Genetic counseling, 68–69, 242, 307, 316
Genetic discrimination, 264–265, 276, 281, 291–292, 297, 307–310, 318
Genetic epidemiology.
See also Geneenvironment interactions adoption studies, 43–44
association studies, 69–70, 78
biological sample collection in
household surveys, 42–43, 51–53
biosocial opportunities in, 332
confounding in, 235
and demogenes, 94–99
and demographic models, 88–89, 94–100, 101–102, 242
developments in, 66
examples of studies, 76
family studies, 68
Human Genome Project and, 72
inheritance patterns of traits, 68–69
origins of human populations, 72
outline of, 66–72
research areas, 67
segregation analysis, 68–69, 77
Genetic exceptionalism, 281
Genetic factors
adoption studies, 43–44
in cardiovascular disease, 48, 50, 73, 74, 78–79, 83, 91, 92–93, 94, 96, 143, 145, 340
in fertility, 46–47
in individual differences in outcomes, 76–81
Genetic linkage, 239, 343, 346.
See also Linkage analysis
Genetic markers.
See also specific types for addiction, 86
closely spaced, 240
as controls, 264
demographic distribution studies, 238–239
family studies, 240–241
incident vs. prevalent outcomes and, 237–238
in population studies, 18, 240, 263–265
for single-gene disease, 140, 238, 314
tightly linked to functional genes, 123
Genetic research
abuses of, 281
agenda on conduct of, 322–323
on archived tissue samples, 281–283
on children, 296–298
cultural considerations, 282–283, 317–319
demographic considerations, 65, 66, 72– 75, 101–102
methods, 70–71
multicultural, multinational setting for, 318–319
responding to change in, 321
Genetic screening, 242, 292, 314, 319
Genetic variance.
See also Alleles in animal models, 217–223
cause of, 66–67
compromise approach, 114
covariance among relatives, 113, 115
and diseases and disorders, 49–50
environment-health interactions and, 48
extent of, 99
functional significance, 5
and health status variance, 67, 77
and individual differences in outcomes, 76–81
major-gene effects, 113
and population differences in outcomes, 84–85, 238
shared genetic effects, 115, 118
Genome
defined, 342
mismatch repair, 139
screening, 240
Genotypes/genotyping
APOE, 30, 50, 60, 73, 74–75, 92, 145
constraint in animal models, 217–219
measurable effects, 114–115, 126
of peripheral blood samples, 145
rare, 77
selective breeding, 225
Geographic distribution of alleles, 72, 141, 148, 238
Geriatric Depression Scale, 167
Germ cell, 342
German Socio-Economic Panel, 2
See also Longevity
GFAP levels, 203
Glucocorticoid levels, 201, 203, 209
Glucose metabolism, 21, 161, 170, 172
Glucose tolerance test, 170
Glycosylated hemoglobin (HbA), 20, 21, 25, 29, 160, 184–185, 254, 256
GNB3 gene, 825T allele, 79, 95
Gompertz-Makeham models, 97
Gonadal atrophy, 142
Great Britain, 22
H
Hair graying and thinning, 142
Haseman-Elston approach, 121
HDL cholesterol, 19–20, 22, 29, 256
Head trauma recovery, 52
Health and Retirement Survey (HRS)
access to database for, 309–310
administrative data linkages, 3, 262
biomarker collection in, 263–264, 265, 267
defined, 343
dementia assessment in, 258, 266, 267
ethical and confidentiality issues, 255
future directions, 271
limitations, 265
self-reports, 262
Health behavior/practices
gender differences in, 254
and lung function, 24
self-reports of, 17
Health Care Financing Administration, 236
Health care usage and availability, 14, 17, 19
Health insurance, 264–265, 276, 281, 291– 292, 307, 313
Health Insurance and Portability and Accountability Act, 308
Health outcomes
bidirectionality of relationships, 14
bioindicators, 14–16
challenge and, 260–262
collection of data on, 12–13
demographic models, 9, 13–14, 76–81, 84–85
dimensions investigated, 11–12
health behavior and, 14
incident vs. prevalent, 237–238
individual differences in, 76–81
longitudinal studies, 12
population differences in, 84–85
risk factors, 15
specification of, 11–12
Health status, genetic component, 67, 77
Hearing Handicap Inventory for the Elderly-Screening Version, 168
Hearing impairment, 167–168
Heart disease, 12, 17, 18, 21, 23, 24.
See also Cardiovascular disease
Height, 3, 15, 204–206, 329–330
Helsinki Aging Study, 88
Hematoxylin, 144
Hemochromatosis, 240
Hepatoma, 197–198
Heritability
fertility and fertility behavior, 46–47
medical disorders, 46, 48, 234
psychological and behavioral phenotypes, 45, 47, 48, 86
scholastic achievement, 47
vocational interests, 47
Heterogeneity, genetic
and age patterns of disease/mortality, 81–82, 139
causes of, 85n.18
in disease risks, 74
in frailty, 75
and genetic epidemiology, 72, 76, 83
in survival analysis, 80–81
unobservable, 80–81
of U.S. population, 142
Heterozygosity, 220–221
High-performance liquid chromatography, 29
Hindus, 140
Hippocampal function, 144
Hispanics, 143
Homeostatic regulatory processes, 22, 134, 170, 221, 343
Homologous structures and processes, 343
Hormones, 172
Household surveys
advisory committee role, 321
bioindicators of health status in, 17–26, 31
collection of data in, 12–13, 16–17, 53–60, 161–162, 236
informed consent in, 279–280, 291
multistate, 291
paternity issues, 292
problems with, 51–53
HPC alleles, 241
Human Genome Project (HGP), 70, 72, 87, 99, 100, 114, 122, 303, 306, 311, 320, 322–323, 343
Human radiation experiments, 278
Human subjects, defined, 284
Huntington chorea, 43, 64, 65, 314
Hyperlipidemia, 170
antioxidants and, 24
gene-environment interactions, 233
heritability of, 46, 95–96, 233
race/ethnicity and, 256
self-reports of, 257
SNS activity and, 23
Hypothalamic pituitary adrenal (HPA) axis, 20, 22–23, 25, 29
I
Identity by state, 139
Idiopathic epilepsy, 46
IGF-1, 205
Immune function, 182, 186, 189, 201, 203, 206, 263
Imputation of missing data, 77, 258
Inanition, 197
Inborn alterations in gene dosage, 139
Inborn errors of metabolism, 151
Inbreeding, 140, 217–219, 221, 222, 223
India, 140
Individual choice, and health outcomes, 14
Individual variability
in health outcomes, 76–81
sources of, 110–111
Indonesia, 271
Inflammation processes, biomarkers of, 19, 20, 21–22, 25
Informed consent
advocacy group brochure, 320
benefits information, 290
for children, 296–298
cognitive function of participants and, 270, 298
for collection of biomarkers, 270, 279– 280
communication of research results, 288–290, 297, 313–314
for demographic data, 279
family contact, 296
federal regulations, 278, 279–281, 289, 296–297, 298, 308, 311
format for forms, 298–299
for genetic research on stored tissues, 146, 149, 277, 280, 281–283, 284
from groups or populations, 319
in household surveys, 279–280
multistage process, 270
in nontherapeutic research, 278–279, 297
ownership of specimens, 295–296
privacy and confidentiality protections, 280–281, 292–293, 297, 308
process, 280–281, 308, 316, 317
project-purpose description, 287–288
purpose of, 277–278
recontacting tissue sources, 276–277, 290, 293–294
repository description, 288
risk considerations, 279–280, 281–283
risk information, 291–292
signing of form for, 278
in therapeutic research, 278, 297
for vulnerable participants, 296–298
withdrawal from protocol, 295
Inheritance patterns.
See also Heritability
association studies of, 69–70
of traits, 68–69
Insect longevity, 184
Institute for Social Research, 251
Institutional review boards (IRBs), 278, 279, 284, 286, 289, 294, 296, 297, 311, 321
Instrumental activities of daily living
Instrumental variables, genes as, 79
Integrated functioning, 162, 168–169, 174, 175
Integrated models, 111, 126–127
Intercellular signaling systems and, 161
Interindividual differences, in aging, 184–185
Interleukin-6 (IL-6), 20, 21, 22, 25, 30
Intermediate variables model, 78n.11
International Genetic Epidemiology Society, 42, 111
Inter-simple sequence repeat PCR, 146
Interview
instruments, 54–55
participation rate, biological sample collection and, 55–56
personal, 235
proxy, 59
time, 56
Interviewers
lay vs. medically trained, 51–52, 53
Invitrogen, 136
Irritable bowel syndrome, 263
Ischemic heart disease, 46, 73, 74, 78–79, 83, 91, 92–93, 94
J
Japan, 94
Japanese Americans, 94
Jewish Chronic Disease Hospital (Willowbrook), 278
K
L
Laboratory assays
for clarification of disease status, 148– 149
CLIA-approved, 289
quality control, 268
reliability and validity, 26
robotic methods, 137
Lactose malabsorption, 72
Language function, 166
Latent effects, 113, 114, 116, 126, 127, 151
LDL cholesterol, 19–20
Life circumstances, indicators of, 14, 19
Life-cycle research approach, 14, 134–138
Life span, 11.
See also Age/aging;
Longevity gender and, 15
genetic factors, 46, 68, 142, 182
height and, 204–206
stochastic events and, 142
Lifestyle factors, 15
Likelihood of adds (LOD) score, 120, 344
Linear regression analysis, genetic information in, 76, 77–78
Linkage analysis, 78
affected sib-pair, 121, 240–241
association methods integrated with, 121, 125
gene mapping with, 120–121
in genetic epidemiology, 70–71, 78
LOD score, 120
longevity studies, 140–142
of pedigree data, 120–121, 140–142, 240– 241
for psychiatric disorders, 86
twin studies, 44–45
Linkage disequilibrium, 71, 98, 120, 123, 139, 222
Liver function, 161
Locus/loci
identical-by-descent, 121, 139
LOD score, 344
quantitative trait, 69, 86, 114, 346
of small effect, 114
SNPs as, 70
Logistic regression analysis, genetic information in, 76, 78
Longevity, 233
antioxidants and, 24
cause-of-death associations, 189, 196– 200, 238
CD8M T-cells and, 187, 191, 192, 193
demographic considerations, 76, 87–88
gene-environment interactions and, 98
genes, 76, 87–88, 97–98, 141–142, 182, 203, 342, 344
natural selection and, 182, 183
in nonhuman species, 182, 183, 184, 196– 197, 198
and reproductive performance, 182–183, 194
segregation analysis, 77
Longitudinal Danish Centenarian Study, 53, 55, 56
Longitudinal Study of Aging (LSOA), 27
Longitudinal Study of Aging Danish Twins (LSADT), 53–54, 55, 56, 59
Longitudinal Study of Middle-Aged Twins, 53, 54, 56, 59
Low-density lipoproteins, 19–20, 24
and cognitive function, 24
health behavior and, 24
measurement, 3, 28, 54, 161–162, 174
M
Mac Arthur Study of Successful Aging, 10
biomarker correlates in, 21, 22, 24, 25
biomedical assessments, 28
cholesterol risk stratification, 20
collection of biological information in, 26–30, 31
cross-cultural comparisons, 255–256
description of, 27–28, 30–31, 262
LSOA compared, 27
physiological measures from blood and urine, 28–30
Macular degeneration, 234
Major affective disorder, 45, 86
Major genes
and age-related risks, 73–74
for blood pressure, 95–96
for BMI, 95
defined, 67
demographic models for, 73–74, 89
disease registries, 239
and genetic variance, 113
interactions in diseases, 74
life-span modulating, 140–142
with multiple disease associations, 74
Mammary carcinoma, 189
Masoro, Edward, 182
Measurable effects
environmental, 116–117
Measurement
of allostatic load, 25
of BMI, 20
error, 26
of gene-environment interactions, 51, 150
Measurement of function
auditory, 168
biological samples, 169, 171–173
blood pressure, 19, 20, 25, 28, 161
cognitive assessment, 28, 54–55, 144, 167
conditions for testing and, 176
criteria for method selection, 175
and diagnosis of disease, 159
in-home methods, 161–162
individual’s role in, 175–176
molecular-level, 160
neuropsychological, 167
observer rating, 175
performance-based, 3, 12–13, 163, 173, 174–175, 176
physiological stress testing, 170
qualitative vs. quantitative, 169–170, 175
respondent burden, 173–174, 297–298
resting vs. challenge, 170–171
at total-organism level, 173–174
types of measures, 171–175
vision, 168
Medical Outcomes Study SF-36, 167
Medical records, 3, 13, 17, 263
Medicare claims records, 3, 13, 149, 251, 252, 258
Mediterranean fruit flies, 184
Mendelian
major factors for disease loci, 120
models of inheritance, 68, 71, 99, 112, 113, 222, 263
Mental health/illness, 11.
See also specific disorders
adoption studies, 234–235
data collection issues, 236
gene-environment interactions and, 44, 86, 241–242
performance testing of, 12
stress and, 260
Mental Health Index, 167
Mental retardation, 49
Messenger RNA (mRNA), 134, 341, 344
and functional capability, 160
microarray screening, 135, 137–138
quantitation, 160
transcription of genes into, 146
Metabolic processes
and allostatic load concept, 25
indicators of health status of, 19–21, 161
Methylation, of gene promoters, 146–147
Mexican Americans, 96
Mice, longevity, 182
Microarray analysis
animal studies, 138
BAC clones, 139
defined, 344
fluorescence-labeled, 136
of gene expression, 120, 133, 135–139, 145, 150, 344
genomic DNA hybridization, 139
for inborn alterations in gene dosage, 138–139
informatics software, 135
oligonucleotide, 135, 136, 139
of pathology tissues, 145, 150
of polymorphisms, 139
resources, 135–137
for special-interest genes, 137
Microelectromechanical systems (MEMS), 3–4
Middle-age populations
advantages of studying, 134, 143–144, 185
Werner syndrome in, 194
Middle East, 140
Midlife in the United States survey
(MIDUS), 271
Migraine headaches, 263
Migrations, population, 123, 124, 235, 238
Ming-Cheng, Chang, 268
Mini-Mental State Examination, 54, 167
Mini-Wright meter, 28
Mitochondrial DNA (MtDNA), 98, 239, 344
Mitochondrial protease, 138
Model, defined, 213–214
Molecular biology, advances in, 64, 66–67
Molecular biomarkers, 134
Molecular screening, 160
Monoclonal antibodies, 145
Monozygotic (identical) twins, 44, 54, 68, 117, 234, 344
Moore v. Regents of the University of California , 295
Morphogens, 344
Mortality
age-related patterns, 76, 81–83, 93
allostatic load and, 25
APOE gene and risk of, 74–75, 78–79, 83, 88, 91–92, 93, 102
BCRA genes and, 91–92
cancer, 84n.15
case-control studies, 75
catecholamine excretion and, 23
coagulation markers, 22
demographic research on, 99
DHEAS and, 23
genetic component, 18, 44, 67, 82
IHD, 93
inflammation markers and, 21–22
initial risks, 200
lung function and, 24
premature death, 44
race/ethnicity and, 102
summary biologic risk scores and, 25
Mortality rate, doubling time, 183, 200
Motion detectors, 161
Motivation, and fertility, 47
Mouse models of aging
advantages over human studies, 209
APOE gene, 225
biochemical mediators of genetic effects, 201, 203
caloric restriction, 187–188, 204, 206–207
cause-of-death associations, 189, 196– 200, 205
CD4M T-cell biomarker, 187–192, 200– 201, 202
CD8M T-cell biomarker, 193
chromosomes,
see Chromosomes, mouse
gender covariate, 188–189, 191–192, 195
gene expression screening, 206–207
genetic control of age-sensitive traits, 200–206
height-life span nexus, 204–206
hormonal exposure/reproductive
history correlation, 191–192
human genome correspondence to, 209
incidence and timing of lethal
conditions, 198–200
longevity mutations, 194–200
methionine restriction, 204
muscle strength correlation, 189, 190
obesity, 205
P-glycoprotein expression, 191, 201, 202
QTL mapping, 194–195, 201, 203
selection pressures on laboratory stocks, 203–204, 205, 207
UM-HET3 population, 195, 200–201
urinary syndrome in, 192, 193, 199, 200
MRFIT study, 89
Multifactorial variance, 69, 126
Multiple comparison problem, 52–53, 70
Multipoint gene mapping, 121
Multistate demographic models, 75, 80
Multivariate logistic regression analysis, 51
Muslims, 140
autosomal dominant, 140, 141, 314
autosomal recessive, 49, 140, 151
at beta amyloid precursor protein locus, 140
of colon cancer cells, 146–147
of cystic fibrosis gene, 99, 314
dominant gain-of-function, 140
heterozygous carriers, 151–152
homozygous, 240
linkage disequilibrium and, 123
in mitochondrial DNA, 239
paternal age and, 139 p53, 294
population age of, 238
protein-truncating, 92
rare, nonrecurrent, 238
sampling strategies, 146
Myocardial infarction, 260
N
National Bioethics Advisory Commission (NBAC), 276, 284, 286, 293, 297, 298, 303, 305
National Breast Cancer Coalition, 320
National Cancer Institute, 148
National Death Index, 13, 236, 251, 252
National Eye Institute Visual Functioning Questionnaire, 168
National Health and Nutrition Examination Survey (NHANES), 10, 27, 89, 168, 257, 271, 277, 289, 332, 344
National Health Insurance exam, 254
National Health Survey of Pakistan, 257, 267
National Heart, Lung and Blood Institute, 299, 312
National Institute on Aging, 2, 27, 162
National Institutes of Health, 284, 286, 297, 320
National Long Term Care Survey (NLTCS), 263, 265
National Medical Expenditure Survey, 174
National Research Council, 304, 305, 318
National Survey of Family Growth, 271
Natural selection, 90, 143, 182, 183.
See also Selective pressures
Nature-nurture debate, 43
Needle biopsy, 173
Nematode worms, 182, 205, 217, 222
Nested case-control studies, 51, 240
Neural network model, 122
Neuroendocrine function, 23
Neuronal cells, 137
Neuroticism, 47
Nicotine, 78n.11
Norepinephrine, 20, 23, 25, 29, 254
Nuclear family studies, 118, 240–241
Nucleic acid probes, 145
Nucleotides, 345
Nun Study, 4–5
O
Observer rating, 175
Occupational exposures to toxic substances, 15
Odense University Hospital, 59
Office for Protection from Research Risks (OPRR), 284, 286, 297, 304, 310–311
Office of Technology Assessment, 304
Oligonucleotides, 135, 139, 345
Online Mendelian Inheritance in Man, 113
Onset of disease, age factors in, 48, 76, 94, 140, 141, 143, 234, 238, 263, 314
Opossum longevity, 182
Organ damage
aging and, 182
detection of, 170
Organ/organoid cultures, 145
Organic acid metabolism, 151
Orofacial birth defects, 236
Osteoarthritis, 74
Osteoporosis, 70, 74, 94–95, 96–97, 142
Ovarian cancer, 91, 92, 93, 237, 320
P
PAH gene, 69n.4
Panic disorder, 86
Parent-offspring pairs, 119, 125, 208
Parent-offspring transmission-based TDT, 125
Parkinson’s disease, 46, 48, 234, 237
Participants, survey/study
for children, 296–298
communication of research results to, 265, 268–269, 288–290, 297, 313–314, 341
familial coercion, 316
family contact, 296
obligations to, 269–271
ownership of specimens, 295–296, 313– 315
partnership role, 320–321
psychological risks to, 315–317
recontacting tissue sources, 276–277, 290, 293–294
risk information, 291–292
vulnerable, 296–298
withdrawal from protocol, 295
Paternal age, and mutations in offspring, 139
Paternalism in medicine, 278
Pathobiology of aging, 15, 146
Pathology samples
autopsy, 148–150
colorectal, 146–147
costs related to, 146
cytological materials, 148
genetic analysis of archived samples, 145–148
organ/organoid cultures from, 145
Peak-flow rate (pulmonary), 20, 24
Pedigree data/studies
blood pressure heritability, 95
confidentiality issues, 309, 313
and gene mapping, 120–121
of genetic association, 143
limitations of, 112
linkage analysis, 120–121, 140–142, 240– 241
for longevity genes, 140–142
population studies and, 235, 236, 240– 241
Peer review, 279
Peptic ulcer, 46
Performance testing, 3, 12–13, 163, 173, 174– 175, 176
Peripheral blood samples, analysis of, 139, 145, 152
Peripheral vascular disease, 21, 50
Personality characteristics
and health outcomes, 14
Phenotypes
selective breeding of animal models, 224–225
senescent, 140–142
Phenylalanine hydroxylase, 49
Phenylketonuria, 49, 69n.4, 151
Phyletic descent, 345
Physical functioning
allostatic load and, 25
antioxidants and, 24
capacity/performance discrepancies, 174
catecholamine excretion and, 23
cognitive function and, 163
components and integration levels, 165– 166
CRP and, 21
defined, 163
DHEAS and, 23
genetic factors, 48
hierarchical framework, 163–165
homocysteine and, 21
IL-6 and, 21
lung function and, 24
performance testing of, 12–13, 54–55, 163, 174–175
summary biologic risk scores and, 25
Physiological functions.
See also Cognitive function
aging and, 143–144, 159–176, 182
cellular, 161
challenge and, 260–262
cholesterol and, 22
differential rates of change, 143–144, 161
home monitoring/assessment of, 161
molecular, 160
neuropsychological, 23, 166–167, 173
organ, 161–162
total organism/integrated, 162, 163–169, 173–174
Physiological measures
APOE genes, 18
from blood and urine, 19, 28–30
in MacArthur Study, 28–30
Pituitary adenoma, 205
Pleiotropic effects, 97, 200, 205, 331, 345
Point estimates, 77
Poisson regression, 77
Polyenvironmental influences, 115–116
Polygenic variance, 69, 86, 113, 222, 223, 345
Polymerase chain reaction (PCR), 137, 345
inter-simple sequence repeat, 146
quantitative reverse transcription-competitive, 137
tissue analysis, 139
Polymorphisms, 67, 70, 72, 84, 85
defined, 345
for longevity, 195
microarray analysis of, 139
single-nucleotide, 67, 70, 72, 99, 100, 120, 139, 346
Population
aging-rate differences within, 194
allele frequencies, 239
bottlenecks, 123
differences, gene studies of, 84–85, 238
ethnohistorical distance between, 84
origins, 72
size, and mutation frequency, 93
stratification, 120, 124, 126, 239
Population-based research and surveys.
See also Cohort studies;
Genetic epidemiology;
Household surveys;
individual studies and surveys
administrative data linked to, 3, 13, 236, 251, 252, 256, 258, 271, 330
animal model research compared, 188
association studies, 239–241
attrition rates, 29, 30, 55–56, 59, 242–243, 270
bioindicator liabilities in, 265–269
bioindicator value in, 254–265
biological specimen collection in, 12–13, 16–17, 26–30, 53–60, 161–162, 207, 236, 242–246, 251
of cognitive function, 11, 150, 237
contamination effects, 265, 268–269, 341
controls, 239
crosswalks in, 271
design challenges, 229, 236–242, 251
of environmental exposures, 230–231, 235, 237–238
familiality and heritability assessment in, 234–236
founder effects/populations, 85, 90, 93, 123, 141, 239, 342
gene-environment interactions, 230, 241–242, 263
gene expression screening in, 207
gene frequencies and disease occurrence, 92–93, 239–241
gene markers in demographically
defined populations, 18, 229, 238–239
genetic bioindicator applications in, 17– 26, 31, 229, 236–242, 263–265
incident vs. prevalent outcomes, 237–238
large-scale, 2, 100–101, 111, 114, 123, 141, 262–263
longitudinal design advantages, 255
methodological issues, 237–238
participation issues, 6, 29, 30, 55–56, 59, 242–243, 251
pathology samples, 134, 150, 151–152
pedigree data from, 235, 236, 240–241
phenotypic outcomes specified in, 231– 234
proxy reports/interviews, 12, 59, 173, 175, 236, 252, 253, 270
public health and clinical applications, 241, 242
representativeness of nonclinical data in, 254–256
sample size considerations, 42, 51, 52, 77, 122, 234, 237, 238, 251
self-reports, 12, 16–17, 26, 30, 174, 175–176, 256–259, 262
spurious associations in, 123–124, 237– 238
Positional cloning, 64, 70, 71, 194, 345
Postal surveys, 235
Power simulation results, 126
Premature death, 44
Preparative cell sorting, 139
Presenilin genes, 101, 140, 141
Privacy of genetic information.
See also Confidentiality issues
Certificate of Confidentiality, 309
on databases, 310–312
discrimination and social stigma
considerations, 264–265, 276, 281, 291–292, 297, 307–310
individual, within families, 310–311
informed-consent protections, 280–281, 291, 292–293, 308–309
medical information distinguish from, 306–307
publication of results and, 309–310
sample identification issues, 283–287, 292–294, 297
Processing speed, 47
Prospective epidemiologic surveys
genetic information in, 88–89
sample size considerations, 237
Prostate cancer, 139, 237, 241
Proteins
age-dependent changes in, 203
beta amyloid precursor, 140–141, 150
C-reactive, 20, 21, 22, 25, 30
eye lens, 201
gene expression modulators, 146
isoforms, 343
physiological modulation role, 134, 146
Proxy reports/interviews, 12, 59, 173, 175, 236, 252, 253, 270
PS-1 gene, 74
PS-2 gene, 74
Psychology
and health outcomes, 14
twin studies, 48
Pubescence, 134
Pulmonary adenosarcoma, 198
Pure-tone audiometry, 168
Q
Qualitative traits
case-control studies for, 123
defined, 66
TDTs for, 124
variability, 110
Quantitative analysis, of gene expression, 139
Quantitative genetic models
basis of, 113
compromise approaches, 114, 116
covariation among relatives in, 113, 115
environmental variance components, 115–117, 125, 127
genetic variance components, 113–115, 127
latent components, 113, 116, 119, 127
major-gene effects, 113
measurable effects, 114–115, 116–117, 127
polyenvironmental influences, 115–116
QTL effects in, 113
sib-pair tests, 125
of variance decomposition, 119
Quantitative reverse transcription-competitive PCR, 137
Quantitative trait loci (QTLs)
allele-sharing methods, 121–122
in animal models, 222, 223, 225
for behavior, 86
for latent genetic effect, 114
mapping, 86, 121–122, 125, 194–195, 201, 203, 222, 322
in mouse longevity studies, 194–195, 201, 203
polygenic influences and, 113, 222
Quantitative traits
continuously distributed, 124
multifactorial variance, 69, 126
variability sources, 110, 112–117
variance component models applied to, 68
Questionnaires, 53–54, 173, 174
R
Race/ethnicity, 76
and Alzheimer’s disease, 94, 142–143
and antioxidant levels, 24
APOE gene and, 18, 79, 85, 92–93, 102, 143
and association studies, 70, 123, 142–143
and blood pressure, 256
and cholesterol, 85
and control selection, 51
and cortisol, 22–23
genetic testing issues, 282–283
and glucose metabolism, 16, 21
GNB3 gene and, 79
and health outcomes, 15–16
and homocysteine metabolism, 21
and SNS activity, 23
Recombinant inbred strains, 223
Recombination, 71, 123, 341, 346
Regression analysis, 51, 88, 122, 124, 188, 191
Reliability
of laboratory assays, 26
of self-reports, 16–17, 26, 257
Religious activities, 22
Renal function, 19, 20, 24, 159, 161, 170, 172, 237, 288
Replicability of studies, 218, 219–220
Repository specimens, 60
commercial use of, 295–296, 311–312
cryopreservation of, 145, 146, 245
defined, 283
informed consent for use of, 270, 276– 277, 279–280, 283, 284, 288
from MacArthur Study of Successful Aging, 29–30, 31
ownership issues, 245, 295, 311–315
recontacting tissue sources, 276–277
risks of genetic testing on, 281–283
samples distinguished from, 283
Representativeness of samples, 55, 118, 119, 218, 219–220, 252
in family studies, 118
self-selection and, 271
Reproduction.
See also Fertility assortive mating, 95, 117, 118, 340
and biomarkers of aging, 191–192
consanguineous matings, 140
longevity and, 182–183, 191–192, 194
postponement of, 138–139
twin studies, 46–47
Resiliency/susceptibility, biological indicators, 18
Restriction fragment length polymorphisms, 120
Reverse causation, 14
Reverse transcriptase, 135, 137
Rhesus monkeys, 200
Rheumatoid arthritis, 46
Risk factors, for poor health outcomes, 15, 19
Risk-taking behavior, 117
Risks, of genetic testing on tissue samples, 281–283
RNA, defined, 346
Rosetta Inpharmatics, 135
Rosow-Breslau scale, 169
Rotterdam Study, 89
S
Samples
coded/linked, 284, 285, 287, 292–293, 297
in genetic epidemiology, 42, 51, 52
of repository specimens, 283
representativeness, 55, 118, 119
size considerations, 42, 51, 52, 77, 122, 208, 237, 238
unlinked, 284, 286, 293, 294, 309
Sampling strategies
bias in, 86, 111, 119, 150, 239, 253
for complex traits, 114
for major-gene effects, 113
mutations in surgical tissues, 146
for sib-pair methods, 122
stratified, 126
surgical pathology tissues, 144–145
Schizophrenia, 44, 45, 48, 86, 234–235
Scholastic achievement in adolescence, 47, 48
Secretary’s Advisory Committee on Genetic Testing, 321
Segregation analysis
applications, 68–69
gene-environment interactions and, 69
in gentic epidemiology, 68–69, 77
of lung cancer risk, 73–74
in mouse models of aging, 194–195
polygenes in, 90
of variance in health outcomes, 77
Selective pressures on laboratory animal stocks, 203–204, 205
Selective sampling, 122
Self-efficacy and control, 23
calibration of, 256–259, 262, 332–333
cognitive status and, 258
of function, 174, 175–176, 258, 332–333
gender differences in, 258
of health behavior, 17
methods, 30
Senescence
defined, 346
immune, 206
phenotypes, 140–142
Sensory function, 167–168, 174
Serum glutamic-oxaloacetic transaminase (SGOT), 29
Sex steroids, 207
Sexuality, 68
Shapiro, Harold, 294
Shared effects
Sib-pair
allele-sharing methods for QTL mapping, 121–122
association studies, 124–125, 143
biological samples, 208
linkage analysis, 121, 240–241
Sibling studies
discordant-sib-pair design, 125
of environmental influences, 126
extension of large-scale surveys, 122
in gene mapping investigations, 119, 121–122
with middle-age cohorts, 144
TDT, 124–125
usefulness of, 112
Sickle-cell anemia, 65, 84, 160, 281
Single-gene diseases, 121, 141
Single-nucleotide polymorphisms (SNPs), 67, 70, 72, 99, 100, 120, 139, 346
Sleep monitoring equipment, 161
Small effect, genes of, 122, 127
Smith, John Maynard, 182
Smith-Lemli-Optiz syndrome (SLOS), 49
Smoking behavior, 116
Snellen Eye Chart, 168
Social integration, 22
Social networks, and health outcomes, 14, 261
Social-psychological characteristics
inflammation markers and, 22
Social Security Administration, 3, 236, 251, 252
Social status variables, heritability of, 86
Social stigma, 297
Social surveys, 238.
See also Population-based research and surveys
biomarker advantages in, 254–265
biomarker liabilities in, 265–266
confirmatory role of, 321
future directions, 271–272
obligations to participants, 269–271
statistical power, 250
Societal functioning, 162–163, 175
Socioeconomic status (SES)
bioindicators of health status related to, 21, 22–23, 24, 25
and fertility, 47
genetic influences, 116
and health outcomes, 14, 15, 22, 47, 260
Somatic cells, 346
Somatic mutations, 90–91, 142, 146, 232
Somatic symptoms of illness, 167
Spatial reasoning, 47
Speech function, 166
Spontaneous activity, 189, 201
Spurious correlations/associations, 70, 98, 100, 126, 222
in genetic association studies, 123–124
Stanford University, 135
Statistical analysis
development of techniques, 64–65, 114
of microarray results, 135, 137
Statistical power, 51, 52, 144, 219, 250
Stereotypes
expectations of aging, 162–163
genetic basis for, 282–283
Stochastic events, 142, 218, 346
Strategene, 136
Stress, 3, 22, 23, 207, 260–262
Study of Health and Living Status of the Elderly in Taiwan.
See Taiwan Study
Study of Women’s Health Across the Nation (SWAN), 27, 271
Summary biologic risk scores, 25–26
Supplement on Aging, 174
Surgical samples, 144–148
Survival analysis
in gene-environment interaction studies, 51
genetic information in, 76, 80–81
heterogeneity in frailty, 76, 80–81
Sympathetic nervous system (SNS) activity, 19, 20, 23, 25, 29
Symptoms of disease, 15
Syntenic linkage, 346
T
T-cell
CD4M, 187–192, 193, 200–201, 206
CD4V, 187
cytokine production, 186
defined, 347
proliferation, 186
Taiwan
National Health Insurance Program, 266
Provincial Institute of Family Planning, 253, 268
Taiwan Study of Health and Living Status
of the Elderly, 27
APOE genotyping in, 264
benefit to participants, 269
biological specimen collection, 253–254, 265, 266–268
cross-cultural comparisons, 255–256
environment-health correlations, 261
informed consent for, 270
self-reports of disease, 257, 262
Tandem mass spectrometry, 151
Tandem repeats, 346
Task Force on Genetic Testing, 304, 305
Tay-Sachs screening, 319
Test of mean differences, 123
Thyroid function/hormone, 161, 194
Tightly linked markers, genetic association using, 123–124
Tissue atrophy, 142
Tissue differentiation during development, 134
Toxicant metabolism, 241
Toxoplasma gondii infection, 151
Transcription factors, 134, 146
Transgenerational environment, 6
Transmission/disequilibrium tests (TDT), 124–125
Tremin Trust, 271
Tumor suppressor genes, 138–139, 142
Tuskegee syphilis experiments, 278
Twin studies
of Alzheimer’s disease, 45
barriers to use of, 65
of behavioral genetics, 45, 48, 68, 86
biases and error sources, 117–118
collection of biological material in, 53–54
of diseases and disorders, 45, 46, 48, 234
equal environment assumption, 45, 117
of familiality, 117–118
of gene-environment interactions, 44–45
generalizability and representativeness of, 118
in genetic epidemiology, 45, 68
of heritability of traits, 44–48, 68, 95, 235
intraclass correlations, 44, 47
of life-span variation, 46, 142
limitations, 112
with offspring, 119
with parents, 119
of reproduction, 46–47
sample size considerations, 234
variance decomposition models, 117
Twins
reared apart, and heritability, 68, 119
registries, 54
types of, 44
Two-dimensional electrophoresis, 134
U
Ultrasound, portable, 162
University of Michigan, 251
University of Southern Denmark, 53
University of Washington, 149
Urinary catecholamine excretion, 23
Urine samples, 19
analytical considerations, 172
collection procedures, 28–30, 254
DNA from, 56
U.S. Department of Defense, 320
U.S. Panel Study on Income Dynamics, 2
V
Validation/validity
of biomarkers of aging, 185–186
of laboratory assays, 26
of self-reports, 257
Variability, in quantitative traits, 112–117
Variable number of tandem repeats (VNTRs), 120, 347
Variance component models, 68, 117, 121– 122, 125
Variance decomposition models, 114, 117, 119
Verbal reasoning, 47
Virginia Commonwealth University, 310–311
Visual function, 167
Visual spatial function, 166–167
Vitamin D receptor (VDR) gene, 70, 74, 96
Vitamin supplements, 24
Vocational interests in adolescence, 47, 48
X
W
Waist/hip ratio, 20, 25, 28, 256
Weibull functions, 82n.13
Welch Allyn Audioscope™, 168
Wellcome Trust, 72
Whispered voice test, 168
Willis, Robert, 333–334
Wisconsin Longitudinal Study, 271
Within-population variation, 80–81
Y
Yeast, 222
Yi-Li, Chuang, 268
Yu-Hsuan, Lin, 268
Z
Zimbabwe, 95n.22
Zygosity misclassification, 118
Zygotes, 347
Zygotic twins, 347
