Cells and Surveys Should Biological Measures Be Included in Social Science Research? (2001) / Chapter Skim
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Demography in the Age of Genomics: A First Look at the Prospects
Demography in the Age of Genomics: A First Look at the Prospects
Pages 64-109
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From page 64... ...
These developments make it easier to associate observed traits (e.g., diseases, risk factors for disease, personality traits, or differences in protein structures) with specific genes.
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From page 65... ...
The third strategy is to include in our analyses data on the genetics of individuals or gene frequencies for populations. Adding genetic information to our analyses could reduce the amount of unobserved heterogeneity and produce estimates of the contribution of specific genes to variations among individuals or across populations.
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From page 66... ...
During the next ten years this might lead to discoveries that will substantially alter demographic research. This paper examines how future research on complex traits made possible by the HOP will affect demography.
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From page 67... ...
The identification of the genes responsible for specific traits then forms the basis for all of the other aspects of the genetic revolution including the promises of medical genetics and the potential future use of genetic information in demographic research. Recent developments will greatly increase the rate of discovery of genes associated with complex traits.
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From page 68... ...
. Until the late 1980s this research was primarily focused on Mendelian models, that is, qualitative traits caused by single genes with a high rate of penetrance.
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From page 69... ...
The Search for Genes Responsible for Specific Traits The study of inheritance patterns only provides evidence that there are genes associated with a given trait. The next step is to identify the specific loci (i.e., locations on chromosomes)
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From page 70... ...
However, recent analyses have demonstrated that whole-genome scans can be efficient methods for identifying genes associated with specific traits even after adjusting for multiple comparisons (van den Oord, 1999~. However, whole-genome scans require a large number of candidate alleles or SNPs, not just candidate genes.
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From page 71... ...
Linkage analysis leads to a candidate region of a chromosome. For example, linkage analysis suggested that there was a gene associated with the risk of Alzheimer's disease (AD)
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From page 72... ...
The mapping of the human genome will provide a very detailed map, thereby increasing the ability to narrow in on the specific loci associated with a given trait. This development, combined with improved statistical methods and expanded computer power, makes possible large-scale searches for the genes associated with complex traits.
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From page 73... ...
Second, we can add genetic information to our statistical models and improve the fit without introducing complex correlations associated with joint causation. The following sections discuss potential applications of demographic models to the study of complex traits, and the use of genetic information in research on standard demographic variables.
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From page 74... ...
The interactions of the two genes can be very complex especially if the gene frequencies differ across populations or the effects of each gene change with age. For example, mutations of the PS-1 and PS-2 genes are associated with very early onset AD (tendon et al., 1997~.
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From page 75... ...
Demographic multistate models will become increasingly important for sorting out the interactions between multiple genes and diseases. POTENTIAL USES OF GENETIC INFORMATION IN DEMOGRAPHIC RESEARCH The recent revolution in genetic epidemiology means that demographers will increasingly have the option of including measured genotypes in their data collection and analyses.
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From page 76... ...
The third area is the potential value of genetic information in research on differences between populations, including cross-national comparisons and differences by race and ethnicity. The fourth section considers how the discovery of genes associated with behavior might change demographic research.
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From page 77... ...
A simple method is to impose estimates of the effects of the genotypes from epidemiologic studies on the analysis of data from a demographic survey. For example, we could adjust observed blood pressure measurements for known differences between genotypes.
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From page 78... ...
However, if demographers are only interested in the link between the behavior and the outcome, there may be little gained by incorporating the genetic risk factors for the behavior since the selectivity associated with the genotype is not apt to be correlated with other behaviors of interest to demographers. 12There is a chance that some genes that cause ill health at early ages might affect social status variables determined at young ages, such as education or marital status.
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From page 79... ...
If sufficient genetic information were available to identify a substantial fraction of those with high risks of health problems, we could replace actual health status with measures of genetic risk of health problems. However, we are rarely interested in controlling for specific health conditions, and overall health status is determined by a large number of genes.
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From page 80... ...
Therefore, the contribution of genetic information to controlling for heterogeneity will depend on the discovery of a few genes associated with a large fraction of the unobserved heterogeneity. Genetic research also might provide evidence of the functional form for the distribution of risks (Weiss, 1990~.
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From page 81... ...
If demographers want to use genetic information to derive functional forms for the distribution of genetic frailty, we may have to tackle that question ourselves. Estimating the distribution of genetic frailty would require combining information on the co-occurrence of risky genotypes, the relative risks of each genotype, and information on how those risks are combined to form total risk.
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From page 82... ...
Therefore, heterogeneity does not have much effect on the hazard rate unless the subgroups have very different risks.l3 For genetic information to explain much heterogeneity, the relative risk associated with the risky genotypes must be large enough to cause a sufficient difference in the absolute risks. In addition, the risky genotypes must be sufficiently common to have a noticeable effect on overall mortal13This ignores changes in functional form associated with averaging hazards functions for the two subgroups.
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From page 83... ...
Therefore, reducing the amount of unobserved heterogeneity will usually require several common risk factors that are each associated with large relative risks. MA noticeable change in population composition was taken to be a drop in the percent in the high-risk subgroup from 50 percent at birth to 40 percent.
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From page 84... ...
Genetic variation within populations does not guarantee differences among populations, so genes that are useful for explaining variation within populations may not explain variation across populations. This has one important implication for identifying genes that might be useful for demographic research.
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From page 85... ...
Genes and Behavior Genes associated with basic personality traits or susceptibility to addictions could help to explain differences in behaviors like risk taking, diet, and use of health services. The potential importance of behavioral genetics, which combines genetics and psychology, is suggested by the fact that an estimated 30 percent of all human genes are expressed primarily in the Cofounder effects occur when migration leads to a population that is descended from a small number of ancestors.
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From page 86... ...
The use of linkage and association studies has produced a number of candidate genes for these disorders, but there have been problems of consistency and replicability of results (Merikangas and Swendsen, 1997~. One area of interest to demographers studying health and behavior is genetic research on addictive behaviors, including smoking and alcohol consumption.
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From page 87... ...
could be falsely linked to polymorphisms that also differ by ethnicity. When behavioral genetics does discover specific genes associated with behaviors, demographic surveys might prove invaluable for putting the results into a social context.
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projections. Prospective Epidemiologic Surveys that Include Genetic Information Some epidemiologic cohort studies of populations have collected genetic information that could be used for demographic research.
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From page 89... ...
The research from these studies is generally limited to the association of APOE genotypes with one outcome. Most of them control only for age and sex, although they rarely provide data by sex unless the differences are statistically significant.20 Many of these studies could be used to study the relative importance of APOE genotype and other risk factors in determining mortality risks.
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From page 90... ...
On the other hand, it is not likely that large numbers of rare mutations of a single gene will cumulate in specific populations without becoming common in any population. Therefore, genes associated with common polymorphisms are much more apt to be useful for explaining variation across populations.
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From page 91... ...
We can apply the four criteria for demogenes to compare the potential usefulness of these genes to demographic research. APOE is Associated with More Common Causes of Death and Disability than the BRCA Genes Table 4-1 shows the associations between polymorphisms of APOE and the risk of IHD mortality and the incidence of AD.
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From page 92... ...
For example, the rate among men aged 65-69 is more than twice as high in TABLE 4-2 APOE Gene Frequencies in Five Populations APOE Genotype e3/3 or e2/4 e3/4 e4/4 e2/3 or e2/2 U.S. whites 65% 21% 2% 13% Italy 71% 17% 1% 11% Finland 59% 31% 4% 6% China 72% 11% 0.4% 16% Nigeria 47% 40% 9% 5%
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From page 93... ...
Mutations of BRCA1 or BRCA2 will not explain much of the variation in breast and ovarian cancer mortality rates across populations. The APOE e4 Allele Is Associated with Larger Attributable Risks than the BRCA Genes The high frequency of the APOE e4 allele combined with high relative risks for IHD and AD leads to a high attributable risk of death.
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From page 94... ...
If there are apt to be a dozen demogenes discovered in the next ten years, then we have to begin planning for the collection of genetic information in demographic surveys. If APOE is apt to be the only true demogene for the next ten years, then genetic information collected in demographic surveys will not have much impact on demographic research in the next ten to twenty years.
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From page 95... ...
Hypertension Twin studies and pedigree studies suggest that the heritability of blood pressure is probably in the range of 25-50 percent (Williams et al., 1994~. However, it is still not clear whether there are one or more major genes for blood pressure.
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From page 96... ...
, ranged between 18 and 69 percent for ten major risk factors for coronary artery disease, including total cholesterol, systolic blood pressure, and body mass index. None of these risk factors appears to be controlled by a single gene, although segregation analyses suggest that there are major unidentified genes for several of these traits.
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Exceptional Longevity One approach to identifying genes associated with low mortality is to examine the genes of those who survive to the oldest ages. Several studies have examined gene frequencies among centenarians or nonagenarians and compared them with frequencies at younger ages.
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Prospects for Demogenes These five conditions are indicative of the state of research on the genetics of complex conditions. Segregation analyses sometimes suggest major genes that would be potential candidates for demogenes.
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This could change as genetic epidemiology discovers genes associated with common conditions. However, in the short run, the flood of new genetic research has led to a more complicated view of the genetics of complex traits.
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From page 100... ...
The Human Genome Project is completing the sequencing of the human genome and is just starting its search for SNPs, and there are still disagreements over the relative advantages of association studies and linkage methods for studying complex traits. The Potential Role of Large-Scale Demographic Surveys in Genetic Research We will almost certainly decide to add the collection of genetic material to large-scale demographic surveys.
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5. Currently available data from epidemiologic surveys could be used to develop models for incorporating genetic information into demographic research.
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From page 102... ...
The old aphorism about "seeing the forest for the trees" may be replaced by "seeing the person (or the ethnic group) for the genes." We will be faced with the problem of putting the flood of genetic information into a social and demographic context.
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From page 103... ...
Gram, and J Jespersen 1999 Longevity is independent of common variations in genes associated with cardiovascular risk.
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From page 104... ...
Neaton 1993 Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease. American Journal of Cardiology 71:160-165.
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Lander, E.S., and N.J. Schork 1994 Genetic dissection of complex traits.
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1997 Genetic epidemiology of coronary artery disease. Epidemiologic Reviews 19~1~:8090.
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From page 107... ...
Sing 1998 An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E Human Genetics 103~2~:234-241.
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Rodriguez 1990 Heterogeneity in demographic research.
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From page 109... ...
American Journal of Human Genetics 65:11781193. Zekraoui, L., J.P.
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