Longitudinal Gompertzian analysis of prostate cancer mortality in the U.S., 1962–1987: A method of demonstrating relative environmental, genetic and competitive influences upon mortality

Age-specific mortality rates for prostate cancer (PC) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-specific PC mortality rate distributions between age 55 and 85 years were determined by a variable competitive factor and a common intersect point. The intersect point for PC occurred at age 61.5 years and mortality rate 27.9 per 100 000 and reflects genetic and environmental influences upon mortality. Between 1962 and 1987, non-age-standardized annual crude PC mortality rates increased 41.6%. Longitudinal Gompertzian analysis suggests that rising PC mortality rates in the United States are the natural consequence of competitive deterministic mortality dynamics. Moreover, longitudinal Gompertzian analysis is a method that demonstrates the relative contribution of environmental, genetic and competitive influences upon disease specific mortality.     

Aging and mortality: manifestations of natural 'non-selection'.

Aging and mortality have long been a source of concern, fascination and investigation. The ultimate question being, why do we age and die? The method of longitudinal Gompertzian analysis demonstrates that aging and mortality are deterministically linked. Moreover, this method of analysis reveals that with enhanced human survival, mortality patterns have changed primarily as the result of the unmasking of latent susceptibilities to other Gompertzian diseases rather than altered environmental etiopathogenic influences. That is, the Gompertzian model of human aging and mortality suggests that redundant programmed failure is the primary reason for ultimate and inevitable mortality. A process by which redundant deterministic disease susceptibilities could accumulate within the genome is natural 'non-selection'. Random genetic mutations which enhance survival until reproduction facilitate the processes of natural selection and evolution. However, random genetic mutations that program for late failure or disease susceptibility would not be eliminated from the gene pool. Thus, random genetic mutations which have programmed for late susceptibility to Gompertzian diseases, and their cumulative non-selection, may be the basis for the deterministic relationship between aging and mortality.     

Longitudinal Gompertzian analysis of lung cancer mortality in the U.S., 1968-1986. Rising lung cancer mortality is the natural consequence of competitive deterministic mortality dynamics

Age-adjusted mortality rates for lung cancer (LC) in the United States from 1968 to 1986 were subjected to longitudinal Gompertzian analysis. Age-adjusted LC mortality rate distributions between age 20 and 50 years were determined by a variable environmental factor and a common intersect point. The environmental factor declined (improved) 1.89-fold for men and 3.11-fold for women in 1986 as compared to 1968. The age at the common intersect point was 47.2 years for men and 39.1 years for women. Between 1968 and 1986, the non-age-standardized annual crude LC mortality rate increased 44.8% for men and 217.6% for women. Longitudinal Gompertzian analysis of LC mortality data suggests that the rising LC mortality rates in the United States are the natural consequence of competitive deterministic mortality dynamics and not a reflection of an environment that is directly more conductive to LC mortality. That is, more people are dying of LC because they are not dying from other diseases such as ischemic heart disease and stroke. Longitudinal Gompertzian analysis demonstrates that single disease mortality should not be studied in isolation, but rather examined in relation to other causes of death. When viewed from this perspective, the basis for the more dramatic rise in LC mortality in women becomes immediately evident.     

Longitudinal Gompertzian analysis of pancreatic cancer mortality in the U.S., 1962-1987: distinguishing between competitive and environmental influences upon evolving mortality patterns.

Pancreatic cancer (PanC) is an extraordinarily lethal neoplasm that is currently the fifth leading cause of cancer death in the United States. Annual age-specific mortality rates for PanC in the U.S. from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-specific PanC mortality rate distributions between age 30 and 60 years were determined by a common fixed intersect point and a variable competitive factor. The intersect point for PanC occurred at age 59.5 years and mortality rate 37.4 per 100,000 for men, and at age 53.2 years and mortality rate 7.9 per 100,000 for women. These intersect points are determined by genetic and environmental influences upon mortality. The observation that these points have remained fixed suggests that there has been no significant alteration in environmental etiopathogenic influences upon PanC mortality. Longitudinal Gompertzian analysis suggests that the emergence of PanC in the U.S. as a significant cause of cancer mortality has been the consequence of competitive influences upon PanC mortality dynamics.     

Longitudinal Gompertzian analysis of emphysema mortality in the US, 1962-1987: the differing basis for evolving mortality patterns in men and women.

Age-specific mortality rates for emphysema in the United States from 1962 through 1987 were subjected to longitudinal Gompertzian analysis, a method that can be used to identify and distinguish aggregate genetic, environmental, and competitive influences upon mortality. Annual crude emphysema mortality rates (per 100,000) among men increased from 11.77 in 1962 to 20.94 in 1968, and then fell to 7.74 in 1987. The basis for this rise and fall is shown to be the corresponding changes in environmental influences upon emphysema mortality in men. Between 1962 and 1987, the annual crude emphysema mortality rates among women increased from 1.71 to 4.25. The basis for the increase of emphysema mortality in women, on the other hand, is shown to be an enhancement of the competitiveness of emphysema as a cause of mortality in women, and not the result of worsening environmental influences. The capability to distinguish between environmental and competitive influences upon evolving human mortality patterns could have a significant impact upon public health policy.     

The dynamics of aging and mortality in the United States, 1900-1988.

The Strehler-Mildvan modification of the Gompertz relationship between aging and mortality provides a dynamic theoretical model for identifying and separating genetic, environmental and competitive influences upon age-related mortality. The initial method of longitudinal Gompertzian analysis, which utilized linear regression, tended to underestimate both genetic and environmental influences upon age-related mortality. A modified method of longitudinal Gompertzian analysis has been applied to mortality due to stomach cancer, cervical cancer and emphysema. This modified method of longitudinal Gompertzian analysis suggests that the genetic influence upon age-related mortality is essentially the same for both men and women. Moreover, application of this modified method suggests that environmental influences upon age-related mortality in the United States have been declining for the past 20 years for men and for the past 45 years for women.     

What does "a gene for heart disease" mean? A focus group study of public understandings of genetic risk factors

There is growing concern in the medical community about potential genetic determinism in the patient population. Limited information about the public understanding of genetic factors in disease formation is available. To access public perceptions of potentially deterministic phrasing of genetic risk factors, we sought to establish interpretations of the phrase, "a gene for heart disease." Focus groups in urban, suburban, and rural communities were conducted from July through October, 2001 in Georgia. A total of 108 participants were recruited. Participants were recruited to balance sex and racial representation. We used three outcome measures for participants understandings of the phrase: (1) participants' statements of the meaning of the phrase; (2) the level of determinism assigned to genetic factors by participants; and (3) participant reports of the health consequences of having "a gene for heart disease." Participants did not report a single interpretation of the phrase. There were dominant participant interpretations under each outcome measure: (1) "a gene for heart disease" was interpreted as meaning genetic and environmental factors both played roles in disease formation; (2) genetic predisposition was perceived as heightened, not absolute, risk; (3) the perceived health impact was a greater risk of becoming sick. Minority interpretations were found under each measure. Overall, naming "a gene for heart disease" does not appear to have a deterministic impact on a plurality of participants' perceptions of risks associated with genetic factors. Genetic fatalism in patient populations may be confined to a sizable minority. Important considerations for provider intervention and patient education are indicated.     

Sociodemographic indicators of stroke mortality

Declining mortality from cerebrovascular disease (stroke) has become a hallmark of cause-specific mortality trends nationwide. Analysis of demographic and socioeconomic characteristics of the population in Allegheny County, western Pennsylvania, in 1980 was carried out to explore their utility as indicators of stroke mortality. Percent black population (followed by unemployment) was found to be the best predictor of stroke mortality in different county areas (r = 0.6, P = 0.001) compared with other variables including income or education. Possible implications for community intervention or primary care programs are discussed.     

Variation in hypertension prevalence in elderly blacks in the United States: the effect of mortality trends

Few controlled studies on the clinical course of hypertension in the elderly have been done, and similar studies are lacking specifically regarding the aging black population. Such studies are indeed difficult considering the complexity of determining the true incidence and prevalence of the disease, the presence of confounding variables such as genetic and environmental influences, and physiologic effects of aging. However, United States vital statistics data on race- and age-specific mortality and morbidity from cardiovascular and cerebrovascular disease are available. The literature has established that hypertension is the principal risk factor and has a direct relationship to the evolution of cardio- and cerebrovascular events. Therefore, examination of these data together with hypertension morbidity could contribute to our knowledge of the prevalence of hypertension in the elderly black population.     

Longitudinal Gompertzian analysis of stroke mortality in the U.S., 1951-1986: declining stroke mortality is the natural consequence of competitive deterministic mortality dynamics

Age-adjusted mortality rates for stroke in the United States from 1951 to 1986 were subjected to longitudinal Gompertzian analysis. Age-adjusted stroke mortality rate distributions were determined by a variable environmental factor and a constant Gompertz slope. Compared to 1951 values, the environmental factor in 1986 had declined (improved) 49.8% for men and 59.1% for women. This was associated with a 51.9% and 31.4% decrease in the annual crude mortality rate from stroke for men and women respectively. However, the Gompertz slope remained remarkably constant from 1951 to 1986; 0.050152 for men and 0.048341 for women. The constant Gompertz slope for age-adjusted mortality rate distributions for stroke is in sharp contrast to the increasing Gompertz slope which occurs with an improving environment in 'degenerative' diseases and aging in general. These findings suggest that the recent dramatic decline in overall stroke mortality is the natural consequence of competitive deterministic mortality dynamics. As the overall environment becomes more conducive to human survival, Gompertzian diseases with converging mortality rate distributions must increase as causes of human mortality at the expense of diseases with constant Gompertz slopes.     

Blood pressure demographics: nature or nurture...... genes or environment?

Hypertension is a growing worldwide problem associated with an increased risk of cardiovascular morbidity and mortality. However, the rates of prevalence of hypertension are higher in some populations than others. Although ethnic and genetic factors have been implied in the past to explain this, the environmental influence and psychosocial factors may play a more important role than is widely accepted. Examining the non-genetic influences in future hypertension research may be necessary in order to clearly define the local blood pressure demographics and the global hypertensive disease burden.     

Genetic and environmental influences on frontal EEG asymmetry and alpha power in 9–10-year-old twins

Modest genetic influences on frontal EEG asymmetry have been found in adults, but little is known about its genetic origins in children. Resting frontal asymmetry and alpha power were examined in 951 9–10-year-old twins. Results showed that in both males and females: (1) a modest but significant amount of variance in frontal asymmetry was accounted for by genetic factors (11–28%) with the remainder accounted for by non-shared environmental influences, and (2) alpha power were highly heritable, with 71–85% of the variance accounted for by genetic factors. Results suggest that the genetic architecture of frontal asymmetry and alpha power in late childhood are similar to that in adulthood and that the high non-shared environmental influences on frontal asymmetry may reflect environmentally influenced individual differences in the maturation of frontal cortex as well as state-dependent influences on specific measurements.     

Genetic Influences on CHD-Death and the Impact of Known Risk Factors: Comparison of Two Frailty Models

The importance of some recognized risk factors on genetic influences for coronary heart disease (CHD) needs further clarification. The aim of the present study was therefore to study the impact of known risk factors on genetic influences for CHD-death. Both twin (correlated gamma-frailty) and non-twin models (univariate gamma-frailty) were utilized and compared regarding their suitability for genetic analyses. The study population consisted of twins born in Sweden between 1886 and 1925. As expected, our findings indicate that genetic influences are important for CHD-death. Inclusion of risk factors in the twin-model increased heritability estimates, primarily due to a substantial reduction in non-shared environmental variances. The genetic influences for CHD-death are only marginally mediated through the risk factors among males, but more so among females. Although the outcome phenotype used in the present study is not behavioral, the analyses demonstrate the potential of frailty models for quantitative genetic analyses of categorical phenotypes.     

Biological aging and Cox hazard analysis of mortality trends in a Mennonite community from south-central Kansas.

This study investigated mortality in 568 individuals from the Goessel Mennonite community in rural central Kansas. There were three main objectives to this research: 1) characterize mortality trends within a biologically well-defined Mennonite community; 2) determine what biochemical, morphological, and physiological risk factors could be related to all-cause mortality, stratified by age and sex; and 3) compare these results to previously described variables that were associated with both biological age and mortality in this population. Mortality data were obtained from three sources: Kansas Vital Records, the Social Security death index, and church records. In total, 221 (39%) individuals were found to have died in this population between January 1980-June 2002. Analogous to the larger US population, the three leading causes of death in this community were heart disease, cancer, and stroke, accounting for 60% of all deaths. Besides advancing age, the greatest biological risk factor in this population was decreased amounts of albumin in men (relative risk, 2.47), potentially indicating underreported cases of either chronic kidney disease or frailty syndrome for males. Cox proportional hazard models demonstrated that increased amounts of total cholesterol may provide a protective effect for elderly individuals. We conclude, based on the previously described heritability of both albumin (h(2) = 0.40) and total cholesterol (h(2) = 0.50) in this population, that underlying genetic factors associated with both chronic degenerative diseases and biological aging may have important implications for understanding mortality patterns in this community.     

The genetic and environmental structure of fear and anxiety in juvenile twins

Fear and anxiety are conceptualized as responses to acute or potential threat, respectively. Adult twin studies found substantial interplay between genetic and environmental factors influencing fear disorders (phobias) and anxiety disorders. Research in children, however, has largely examined these factors independently. Thus, there exists a substantial knowledge gap regarding the underlying etiologic structure of these closely‐related constructs during development. Symptom counts for five fear (criticism, the unknown, death, animal, medical) and four anxiety (generalized, panic, separation, social) dimensions were obtained for 373 twin pairs ages 9–14. Multivariate twin modeling was performed to elucidate the genetic and environmental influences distributed amongst these dimensions. The best fitting model contained one genetic, two familial environmental, and two unique environmental factors shared between fear and anxiety symptoms plus dimension‐specific genetic and unique environmental factors. Although several environmental factors were shared between fear and anxiety dimensions, one latent factor accounted for genetic influences across both domains. While adult studies find somewhat distinct etiological differences between anxiety and phobic disorders, the current results suggest that their relative genetic and environmental influences are not as clearly demarcated in children. These etiological distinctions are more nuanced, likely contributing to the highly diffuse symptom patterns seen during development.     

Quantitative genetic analysis of IQ development in young children: Multivariate multiple regression with orthogonal polynomials

The study of psychological development has recently benefited from innovative analytic methods for estimating and examining the correlates of individual growth curves. These methods are more consistent with a conceptualization of development as an ongoing, continuous process, rather than as increases or decreases in a trait between two discrete time points. Recent developmental behavior genetic models have focused on continuity and change in the genetic and environmental influences underlying phenotypes. In contrast, we present a model for genetic and environmental influences on phenotypic development per se. In this model, we adapted multiple regression methods developed for twin designs (DeFries and Fulker, 1985) to a parent-offspring adoption design and to a multivariate framework in which repeated measurements are decomposed into orthogonal polynomial trends. We applied these analyses to the development of IQ during infancy and early childhood using parent-offspring data from adoptive and nonadoptive families in the Colorado Adoption Project. The results suggested familial environmental influences on children's mean IQ for ages 1–4 but environmental influences specific to fathers' cognitive ability on children's IQ development. We also discuss advantages and disadvantages of the multivariate multiple regression method for studying genetic and environmental influences on development.     

A modified cohort method for secular trend analysis: heart disease mortality in the USA 1914-1963 and follow-up to 1983

The principles behind the analysis of secular trends of cause-specific mortality rates by 'current' and 'cohort' methods were subjected to theoretical examination. A more general method, named here the 'midpoint' method, was found for which the 'current' and 'cohort' methods are special types of limiting cases. It is shown that the span of time over which the causes of disease act, and the period of life, whether early or late, in which they are predominantly concentrated will determine which of these three methods is appropriate for each specific cause of death. For 'cumulative' diseases (of which atherosclerosis and hypertension are thought to be examples), defined as diseases which accumulate slowly over the greater part of a lifetime under the influence of etiologic factors that are widely dispersed in time, the data favor the 'midpoint' method as the most appropriate one of the three. Secular trends in diseases of the heart in the USA from 1914 - 1963 were examined in 1968 by this method, thus generating predictions about the trends to be expected after 1963. Although no definitive conclusion could be reached at that time, the probabilities then favored the hypothesis that the etiologic forces which contribute to heart disease mortality reached a peak around 1930 or earlier, and that the subsequent decline had not yet given evidence of ending. Predictions of secular declines in mortality rates attributed to diseases of the heart made in 1968 are compared here with the subsequent 20 years of experience by specific age-race-sex groups. Validation of the midpoint cohort method of analysis is claimed. The peak in heart disease mortality that occurred in 1968 is seen as a temporary fluctuation within the grand pattern of 20th Century USA.     

Major depression and life satisfaction: A population-based twin study

BackgroundThe extent to which positive and negative indicators of mental health share etiological influences has been studied to a limited degree only. This study examines the genetic and environmental influences on association between liability to lifetime DSM-IV Major Depressive Disorder (MDD) and dispositional life satisfaction (LS).MethodsTwo-wave questionnaire data on LS (assessed 6 years apart) and lifetime MDD obtained by structured clinical interviews in a population-based sample of adult twins were analysed using structural equation modelling in Mx.ResultsThe prevalence of lifetime MDD was estimated to be 11.1% and 15.8% in males and females, respectively. Individuals fulfilling the criteria for MDD reported significantly lower levels of LS. The co-variation in MDD and dispositional LS was found to be accounted for by genetic and unique environmental influences only. The phenotypic correlation was estimated to be 0.36, of which genetic influences accounted for 74% and environmental factors the remaining 26%. The correlation between genetic factors for MDD and LS was estimated to be ?0.55 and the correlation between unique environmental factors to be ?0.22. Heritability was estimated to 0.34 and 0.72 for MDD and LS, respectively.LimitationsThe sample consists of twins only and there are limitations associated with the twin design.ConclusionsWhereas genetic influences on vulnerability to lifetime MDD are considerably shared with liability to (low) LS, environmental influences are more distinct. Thus, environmental factors associated with risk of MDD do not strongly impact on dispositional LS, and conversely, environmental factors influencing dispositional LS do not strongly buffer against MDD.     

Covariation of psychosocial characteristics associated with cardiovascular disease: genetic and environmental influences

OBJECTIVE: Three psychosocial characteristics associated with cardiovascular disease (CVD)-depression, hostility, and social support-tend to correlate with one another. However, the causes of each characteristic and why they tend to co-occur are not completely understood. Therefore, the current study used a twin design to examine the relative contributions of genetic and environmental influences to the variation and covariation of these three psychosocial characteristics. METHODS: The sources of variation and covariation among the Beck Depression Inventory, the Cook-Medley Hostility Scale, and the Interpersonal Support Evaluation List were examined in a young adult community sample of 157 monozygotic and 75 dizygotic twin pairs. RESULTS: Phenotypic confirmatory factor analysis indicated that a single latent factor could account for their moderate intercorrelations. Twin analyses indicated that the Beck Depression Inventory and Interpersonal Support Evaluation List were each influenced by genetic and nonshared environmental factors, whereas the Cook-Medley Hostility Scale was influenced by familial (genetic and/or shared environmental) and nonshared environmental factors. Bivariate associations between these scales were largely determined by common genetic effects and, to a lesser degree, common nonshared environmental effects. Covariation among the three scales could be explained by a single common genetic factor and a common nonshared environmental factor. Environmental factors shared within families did not contribute to covariation among the psychosocial characteristics. CONCLUSIONS: The results challenge the conventional approach of examining these psychosocial variables as independent risk factors for cardiovascular disease and argue for the importance of investigating specific causes for their covariation.     

Contribution of malformations and genetic disorders to mortality in a children's hospital

Malformations and genetic disorders are the leading cause of infant mortality in the US. Many malformations have a genetic basis due to genic, chromosomal, or multifactorial causation. We have studied the proportion of pediatric cases in a university-affiliated children's hospital that died of malformations and genetic disorders. We reviewed, retrospectively, deaths over a 4 year period (1994-1998) at Primary Children's Medical Center (PCMC), a university-affiliated tertiary children's referral hospital in Utah. The age at death and the cause of death were recorded for each case. We analyzed 523 cases; 180 (34.4%) deaths were due to malformations and genetic disorders. Of those 180, 30 (16.7%) had chromosome anomalies, 21 (11.7%) had a recognizable malformation syndrome, 118 (65.6%) had a malformation of unknown cause, and 11 (6.1%) had some other genetic disorder. One hundred and twenty-two (23.3%) deaths were due to trauma (accidental and non-accidental). Seventy-nine (15.1%) deaths were due to short gestation or perinatal complications. Forty-five (8.6%) deaths were due to an infectious disease and 45 (8.6%) from neoplasms. Thirteen (2.5%) were diagnosed for sudden infant death "syndrome." Twelve (2.3%) patients with malformations and/or genetic disorders died of an acquired condition not clearly related to the underlying disorder. Seven (1.3%) patients died of an unknown cause and 20 (3.8%) patients died of other specified conditions. In addition, 51.0% patients (age <1 year) died of a malformation and/or genetic disorder. Genetic disorders and malformations are a substantial cause of mortality in a referral pediatric hospital. Knowledge of the impact of genetic diseases on mortality is important for the integration of preventive measures and health care strategies to care effectively for patients and their families. This information emphasizes the importance of further study of whether or not early recognition influences mortality rate and management.