National Academy Of Sciences-National Research Council Research Articles

The NAS-NRC Twin Registry and Duke Twins Study of Memory in Aging: An Update.

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917-1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson's disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).

Heritability of usual alcohol intoxication and hangover in male twins: the NAS-NRC Twin Registry.

Alcohol consumption is influenced by heritable factors. The genetic influence on usual high-density drinking, including alcohol intoxication and hangover, is unknown. We aim to estimate the heritability of usual high-density drinking. A total of 13,511 male twins in this cross-sectional study were included from the National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry. Data on the frequency of alcohol intoxication and alcohol hangover over the past year, that is, usual high-density drinking (phenotypes), were collected through a self-administered questionnaire when twins were middle-aged in 1972. Structural equation modeling was used to estimate the variance components of phenotypes. The mean of the frequency of usual high-density drinking in the entire twin population was 0.16 times per month for intoxication and 0.18 times per month for hangover. The heritability of usual alcohol intoxication was 50.7% (95% confidence interval [CI] 46.2 to 55.0) before and 49.9% (95% CI 45.3 to 54.2) after the body mass index (BMI) adjustment. The heritability of usual hangover was 55.4% (95% CI 51.2 to 58.6) before and 54.8% (95% CI 50.6 to 58.8) after adjustment for BMI. Unshared environmental factors between co-twins explained the remaining variance in alcohol intoxication and in hangover. Both genetic and unshared environmental factors have important influences on usual alcohol intoxication and hangover. These findings are important in understanding the occurrence of and developing interventions for usual high-density drinking.

Update on the NAS-NRC Twin Registry

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II. This article updates activity in this registry since the earlier 2002 article in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related macular degeneration, and primary osteoarthritis were published, as well as articles based on previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier collected risk factor data from questionnaires. Examination data from the subset of National Heart, Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship of endogenous sex hormones to coronary heart disease and morphological changes in aging brain structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of the registry is being made.

Duke Twins Study of Memory in Aging in the NAS-NRC Twin Registry

AbstractThe Duke Twins Study of Memory in Aging is an ongoing, longitudinal study of cognitive change and dementia in the population-based National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry of World War II Male Veterans. The primary goal of this study has been to estimate the overall genetic and environmental contributions to dementia with a specific focus on Alzheimer's disease. An additional goal has been to examine specific genetic and environmental antecedents of cognitive decline and dementia. Since 1989, we have completed 4 waves of data collection. Each wave included a 2-phase telephone cognitive screening protocol, followed by an in-home standardized clinical assessment for those with suspected dementia. For many participants, we have obtained postmortem neuro-pathological confirmation of the diagnosis of dementia. In addition to data on cognition, we have also collected information on occupational history, medical history, medications and other lifetime experiences that may influence cognitive function in late life. We provide an overview of the study's methodology and describe the focus of recent research.

Update on the NAS-NRC Twin Registry

AbstractThe National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II. This article updates activity in this registry since the earlier 2002 article in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related macular degeneration, and primary osteoarthritis were published, as well as articles based on previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier collected risk factor data from questionnaires. Examination data from the subset of National Heart, Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship of endogenous sex hormones to coronary heart disease and morphological changes in aging brain structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of the registry is being made.

Duke Twins Study of Memory in Aging in the NAS-NRC Twin Registry

The Duke Twins Study of Memory in Aging is an ongoing, longitudinal study of cognitive change and dementia in the population-based National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry of World War II Male Veterans. The primary goal of this study has been to estimate the overall genetic and environmental contributions to dementia with a specific focus on Alzheimer's disease. An additional goal has been to examine specific genetic and environmental antecedents of cognitive decline and dementia. Since 1989, we have completed 4 waves of data collection. Each wave included a 2-phase telephone cognitive screening protocol, followed by an in-home standardized clinical assessment for those with suspected dementia. For many participants, we have obtained postmortem neuropathological confirmation of the diagnosis of dementia. In addition to data on cognition, we have also collected information on occupational history, medical history, medications and other lifetime experiences that may influence cognitive function in late life. We provide an overview of the study's methodology and describe the focus of recent research.

Verification of Self-Report of Zygosity Determined via DNA Testing in a Subset of the NAS-NRC Twin Registry 40 Years Later

AbstractThe National Academy of Sciences — National Research Council (NAS-NRC) twin panel, created nearly 50 years ago, had twin zygosity determined primarily via a similarity questionnaire that has been estimated to correctly classify at least 95% of twins. In the course of a study on the genetics of healthy ageing in the NAS-NRC twins, DNA was collected for genome-wide scanning and zygosity confirmation was examined in 343 participating pairs. The sample was supplemented from two other studies using NAS-NRC twins where one or both co-twins were suspected to have Alzheimer disease or another dementia, or Parkinson's disease. Overall 578 twin pairs with DNA were analyzed. Zygosity assignment for 96.8% (519/536) was confirmed via questionnaire. Among 42 pairs whose questionnaire responses were inconclusive for assigning zygosity, 50% were found to be monozygous (MZ) and 50% were dizygous (DZ). There was some evidence for greater misclassification of presumed DZ pairs in the healthy ageing study where participation favored pairs who were similar in having a favorable health history and willingness to volunteer without any element of perceived risk for a specific disease influencing participation.

Verification of Self-Report of Zygosity Determined via DNA Testing in a Subset of the NAS-NRC Twin Registry 40 Years Later

The National Academy of Sciences -- National Research Council (NAS-NRC) twin panel, created nearly 50 years ago, had twin zygosity determined primarily via a similarity questionnaire that has been estimated to correctly classify at least 95% of twins. In the course of a study on the genetics of healthy ageing in the NAS-NRC twins, DNA was collected for genome-wide scanning and zygosity confirmation was examined in 343 participating pairs. The sample was supplemented from two other studies using NAS-NRC twins where one or both co-twins were suspected to have Alzheimer disease or another dementia, or Parkinson's disease. Overall 578 twin pairs with DNA were analyzed. Zygosity assignment for 96.8% (519/536) was confirmed via questionnaire. Among 42 pairs whose questionnaire responses were inconclusive for assigning zygosity, 50% were found to be monozygous (MZ) and 50% were dizygous (DZ). There was some evidence for greater misclassification of presumed DZ pairs in the healthy ageing study where participation favored pairs who were similar in having a favorable health history and willingness to volunteer without any element of perceived risk for a specific disease influencing participation.

The Association Between Prolonged Fatigue and Cardiovascular Disease in World War II Veteran Twins

Reports of fatigue preceding cardiac events have recently been confirmed by large prospective studies. To assess for genetic confounding, we investigated prolonged fatigue and cardiovascular disease (CVD) in a cohort of World War II veteran twins. We examined data from a questionnaire mailed to members of the National Academy of Sciences-National Research Council (NAS-NRC) World War II Twins Registry in 1998 and 1999 which included questions on demographics, medical conditions and symptoms of fatigue. Data from twins discordant for prolonged fatigue lasting a month or more were analyzed using conditional logistic regression. Among 1955 twin pairs, 157 monozygotic and 174 dizygotic pairs (mean age 74 years) were discordant for prolonged fatigue. An association was found between prolonged fatigue and a history of myocardial infarction or coronary artery surgery adjusting for age, socioeconomic status, smoking, alcohol use and depression (OR [Odds Ratio]: 2.2; 95% CI: 1.3-4.0). When analyses were performed separately by zygosity, the association was slightly larger for monozygotic (OR: 3.3; 95% CI: 1.2-9.1) than dizygotic twins (OR: 1.9; 95% CI: 0.9-4.0). These data corroborate the association of fatigue with CVD and suggest that it is not influenced by a common genetic factor. Further studies are needed to clarify the relationship and to better understand the biologic mechanisms.

Cancer risk assessment of toxaphene.

The primary purpose is to do cancer risk assessment of toxaphene by using four steps of risk assessment proposed by the United States National Academy of Sciences/National Research Council (NAS/NRC). Four steps of risk assessment including hazard identification, dose-response relationship, exposure assessment, and risk characterization were used to evaluate cancer risk of toxaphene. Toxaphene was the most heavily used insecticide in many parts of the world before it was banned in 1982. It increased incidence of neoplasms of liver and uterus in mice and increased incidence of neoplasms of endocrine organs, thyroid, pituitary, adrenal, mammary glands, and reproductive systems in rats. From mice's and rats' study, slope factor for toxaphene is 0.8557 (mg/ kg/day)(-1). Lifetime average daily dose (LADD) of toxaphene from ambient air, surface water, soil, and fish were 1.08 x 10(-6), 5.71 x 10(-6), 3.43 x 10(-7), and 7.96 x 10(-5) mg/kg/day, respectively. Cancer risk of toxaphene for average exposure is 7.42 x 10(-5). From this study, toxaphene might have carcinogenic risk among humans.

A Latent Variable Approach to Studying Risk Factors for Alzheimer’s Disease

The objective of this study is to investigate and to improve measurements for the study of suspected animal and occupational exposure risk factors for Alzheimer’s disease (AD). A subsample (n = 200) of a longitudinal study sample from research on risk factors for Alzheimer’s disease was selected by systematic probability sampling. Participants were men born between 1917 and 1927, selected from the National Academy of Sciences-National Research Council (NAS-NRC) Registry of white male twins who served in the United States Armed Forces during the World War II Korean Conflict era. A questionnaire was administered via telephone interview. A total of 25 animal exposure items and 28 occupational exposure items were selected from the risk factor questionnaire administered to the men. Measurement for animal or occupational exposure was ascertained based upon the participants’ responses to the survey questions. Latent variable analyses extracted 3 animal exposure factor scales: pet, farm/livestock and exposure to wild animals (e.g. while hunting). The occupational exposure data led to extraction of 2 factor scales: medical exposures and manual work involving metal. Latent variable analysis revealed that many items (potential risk factors) are highly correlated with each other and can be conceptualized as correlated observable manifestations of more unitary underlying constructs. In future research, it may be advantageous to assess correlated items such as these in relation to an underlying dimension of exposure, rather than as discrete exposures.

Genetic predisposition to organ-specific endpoints of alcoholism.

Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z, and Omenn, G. S., Alcohol. Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum-likelihood modeling indicated that approximately 50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.

The radiation effects research foundation of Hiroshima and Nagasaki. Past, present, and future

THE ATOMIC Bomb Casualty Commission (ABCC) was established in Hiroshima in 1947 and in Nagasaki in 1948 by the US National Academy of Sciences, National Research Council (NAS/NRC) based on President Truman's directive to initiate a long-term and comprehensive epidemiological and genetic study of the atomic bomb survivors.¹The Japanese National Institute of Health under the Ministry of Health and Welfare joined the ABCC 1 year later to assist in the studies and improve the cooperation of the survivors. This arrangement continued for 28 years until it was replaced in 1975 by the Radiation Effects Research Foundation (RERF), a nonprofit Japanese foundation binationally managed and supported with equal funding by the governments of Japan, through the Ministry of Health and Welfare, and the United States, through the NAS/NRC under contract with the US Department of Energy (and its predecessors). Thanks to the cooperation of the survivors and the contributions

The Radiation Effects Research Foundation of Hiroshima and Nagasaki

THE ATOMIC Bomb Casualty Commission (ABCC) was established in Hiroshima in 1947 and in Nagasaki in 1948 by the US National Academy of Sciences, National Research Council (NAS/NRC) based on President Truman's directive to initiate a long-term and comprehensive epidemiological and genetic study of the atomic bomb survivors.1The Japanese National Institute of Health under the Ministry of Health and Welfare joined the ABCC 1 year later to assist in the studies and improve the cooperation of the survivors. This arrangement continued for 28 years until it was replaced in 1975 by the Radiation Effects Research Foundation (RERF), a nonprofit Japanese foundation binationally managed and supported with equal funding by the governments of Japan, through the Ministry of Health and Welfare, and the United States, through the NAS/NRC under contract with the US Department of Energy (and its predecessors). Thanks to the cooperation of the survivors and the contributions

Self-reported alcohol intake and cognition in aging twins.

To determine the relationship between long-term alcohol intake and cognitive functioning in aging Caucasian men. A retrospective cohort and co-twin-control study of self-reported alcohol intake and cognitive testing using the National Academy of Sciences-National Research Council (NAS-NRC) Twin Panel of U.S. veterans (born between 1917 and 1927). The study included 4,739 twins with two self-reported drinking histories (1970s and 1980s) and a telephone mental status interview (1990 and 1991) that also included 145 individuals with a diagnosis of alcoholism. Age and education adjusted cognitive scores were lower (p < .05) in diagnosed alcoholics than in the remainder of the subjects. To compare age and education adjusted cognitive scores in alcohol intake, the 4,739 twins were divided, based upon questionnaire data, into nondrinkers and 5 quintiles of drinkers by average reported drinks of alcohol weekly (< 1.0, 1-3.3, 3.4-8.1, 8.2-16.0, > 16.0). Past drinkers had scores lower (p < .05) than nondrinkers and all but quintiles 1 and 5 of the drinkers. The light drinkers in quintile 1 and the heavy drinkers in quintile 5 scored lower (p < .05) than the moderate drinkers in quintile 4. Monozygotic twins in quintile 4 scored higher (p < .05) than their co-twins in quintiles 1-3. No evidence was found to indicate an association between moderate long-term alcohol intake and lower cognitive scores in aging individuals. There was a suggestion of a small protective effect of past moderate alcohol intake on cognitive function with aging.

The National Academy of Sciences--National Research Council Veteran Twin Registry.

With recent advances in molecular biology and genetics, cohorts such as the National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry may become of increasing importance. This paper outlines the creation and history of the NAS-NRC Twin Registry, methodologies utilized for analysis of twin data, studies that have been completed or are underway, and possible future types of studies.

Effect of Dietary Calcium on Colon Carcinogenesis Induced by a Single Injection of 1,2-Dimethylhydrazine in Rats

The purpose of this study was to determine if high levels of dietary calcium could inhibit the induction of colon tumors in rats injected with a single dose of 1,2-dimethylhydrazine (DMH). Rats were given a single subcutaneous injection of DMH (200 mg/kg body weight) 2 wk before they were fed purified diets containing 5% fat and four different levels of calcium (as calcium gluconate). After 8 mo, the following incidences of colon tumors (total) were seen: 0.2% Ca, 56%; 0.5% Ca [National Academy of Sciences/National Research Council (NAS/NRC) recommended level], 75%; 1.0% Ca, 61%; 2.0% Ca, 41%. Thus, rats fed calcium at levels above or below the NAS/NRC recommendation had lower tumor incidences. The total tumor incidence and the incidence of adenocarcinomas (with or without invasion) were not significantly affected by calcium, but the incidences of benign adenomatous polyps and of distal colon tumors were significantly affected. Autoradiographic examination of [3H]thymidine-treated rats revealed that the level of calcium did not significantly alter the cell kinetic indices in the distal colon. In the proximal colon, however, the 0.2% Ca group had a significantly larger proliferative zone, with significantly more labeled cells present at the bottom of the colon crypt. Mineral analysis of tibias and serum samples revealed that rats fed higher levels of calcium had lower bone Fe and serum Mg contents, but no significant trends were seen for Ca, P, Zn or Cu. Therefore, increasing or decreasing the calcium content above or below the NAS/NRC recommendation (supplemented to low fat diets) during the promotional phase of colon carcinogenesis altered the tumor incidence, but the effect was confined to the distal colon and to benign adenomatous polyps.

Burke new Tectonics editor

Kevin C. Burke, National Academy of Sciences/ National Research Council (NAS/NRC), assumed responsibilities as Editor in Chief of the American Geophysical Union (AGU) journal Tectonics at the beginning of 1990, taking over from Raymond A. Price, Queens University, Kingston, Ontario. Asger Berthelsen, University of Copenhagen, Denmark, continues as the European Editor, and Paul F. Hoffman, Geological Society of Canada, assumes the task of North American Editor. Tectonics is a joint publication of AGU and the European Geophysical Society.

The National Research Council Committee on Human Factors

The Committee on Human Factors, a standing committee of the National Academy of Sciences/National Research Council (NAS/NRC), advises its sustaining sponsors and other requesting organizations on issues involved in the design of socio-technical systems and on the research and methods needed to help enhance their operability and safety. This paper describes the origins, purposes, operations and program of the committee and emphasizes the special attributes of this and other NAS/NRC commtittees.

The Use of Animals in Research

The Use of Laboratory Animals in Biomedical and Behavioral Research, the report of the National Academy of Sciences-National Research Council (NAS-NRC) has now been released. 1 was on the committee that authored the report and fully concur with it as far as it went. It is no mean task to agree on reasonable and comprehensible standards for the humane treatment of animals in research. Nonetheless, in my view, there is something missing: the committee slighted what I believe is the most important practical aspect of the issue of “animal rights”—the political dimension. Biomedical research is now under serious political attack from a variety of organizations and individuals who, for ideological reasons, desire to stop or drastically reduce the use of animals in experimentation, and they are willing to use virtually any tactics to achieve this goal. They rarely state this aim, or pursue it directly, perhaps because this would lead to an open discussion of all the benefits and costs involved in biomedical rese...