ABSTRACT IMPACT: The findings of this study could lend us insights into behavioral intervention that could potentially prevent or slow the onset of Alzheimer’s disease. OBJECTIVES/GOALS: This study examines the association between cognitive and physical resilience and Alzheimer’s disease in a Tibetan Buddhist monastic community in southern India. METHODS/STUDY POPULATION: The study will employ mixed methods of semi- and unstructured interviews and surveys. The interviews will be conducted among 60 monks of age 50+ in six Tibetan monastic colleges in southern India. The interviews will comprise general questions related to monks’ monastic educations and practices, as well as clinical cognitive interviews. Interviewees will be randomly sampled from a census of monks at the six monasteries. Owing to COVID-19 crisis, we will begin data collection, starting with interviews via zoom in mid-December 2020. The survey, which includes demographic information, cognitive assessments, meditative practices, health, memory and physical activity, will be conducted among 400 monks. The survey will be performed onsite and is tentatively scheduled in the summer of 2021. RESULTS/ANTICIPATED RESULTS: The study will help to identify factors associated with physical and cognitive resilience and develop measures to quantify and describe meditative and cognitive practices. These data will be used to both adapt validated measures developed in Western populations for use with this unique population and to develop new items on physical and cognitive resilience to include in the planned survey. Furthermore, the study will provide information about the prevalence of Mild Cognitive Impairment and Alzheimer’s disease and related dementias in this population and development of the survey to capture culturally appropriate measures, including on meditation. The findings could eventually lend us insights into behavioral intervention that could potentially prevent or slow the onset of Alzheimer’s in wider population. DISCUSSION/SIGNIFICANCE OF FINDINGS: Cognitive and physical resilience are understood to confer significant benefits to health outcomes and healthy aging. However, the factors related to resilience, particularly in older adults, are poorly understood. This study will estimate the link between frequency and intensity of meditative practices and physical and cognitive resilience.

In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

The International Network of Twin Registries (INTR) aims to foster scientific collaboration and promote twin research on a global scale by working to expand the resources of twin registries around the world and make them available to researchers who adhere to established guidelines for international collaboration. Our vision is to create an unprecedented scientific network of twin registries that will advance knowledge in ways that are impossible for individual registries, and includes the harmonization of data. INTR will also promote a broad range of activities, including the development of a website, formulation of data harmonization protocols, creation of a library of software tools for twin studies, design of a search engine to identify research partners, establishment of searchable inventories of data and biospecimens, development of templates for informed consent and data sharing, organization of symposia at International Society of Twin Studies conferences, support for scholar exchanges, and writing grant proposals.

The University of Washington Twin Registry is a unique community-based registry of twin pairs who join specifically to participate in scientific research. It was founded in 2002 to serve as a resource for investigators throughout the scientific community. Current enrollment exceeds 7,200 pairs, and plans are in place to increase enrollment to 10,000 pairs by 2015. In addition to serving as a recruitment base for new research studies, the registry maintains extensive and continually expanding survey data on physical and mental health, as well as a biorepository that includes DNA from more than 8,800 individual twins. The registry is engaged in linking member data to birth records and to diagnostic and procedure variables for hospital-based care provided to members in Washington State. It also incorporates several innovative variables relevant to the built and social environments, which were created by geocoding twin addresses and linking the resulting coordinates to geospatial information systems databases. This combination of existing data and biospecimens, characterizing a group of twins who are willing to participate in research, is a valuable resource for the new wave of twin studies. These include ‘omics’, epigenetics, gene-by-environment interactions, and other novel methods to understand human health.

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue are conditions of unknown etiology. The Centers for Disease Control and Prevention (CDC) define CFS as an illness characterized by ≥ 6 months of disabling fatigue associated with muscle pain, pharyngitis, and alterations in mood, sleep and neurocognition. We constructed a registry of twins with chronic fatigue to facilitate research on the impact of illness, the associated medical and psychosocial factors, and the heterogeneous proposed mechanisms for these conditions. We have recruited 204 twin pairs in which one or both members reported persistent fatigue through patient support group newsletters (60%), clinicians/researchers familiar with CFS (12%), notices placed on electronic bulletin boards for CFS (11%), twin organizations and researchers (6%), relatives and friends (3%) and other sources (8%). Complete data are available for 177 pairs (87%). Twins completed an extensive questionnaire booklet that included measures of physical and mental health, functional status, and psychosocial factors; a structured psychiatric interview was also conducted by telephone. Twins were classified using three increasingly more stringent diagnostic criteria for chronic fatigue: 1) ≥ 6 months of fatigue (115 discordant and 61 concordant pairs); 2) chronic fatigue with additional symptoms and application of the medial exclusions of the CDC CFS case definition as obtained by self-report (92 discordant and 41 concordant pairs) and; 3) chronic fatigue with additional symptoms unexplained by self-reported medical conditions and psychiatric diagnoses as determined by the structured interview (69 discordant pairs and 25 concordant pairs). Despite the limitations of a volunteer registry, the Chronic Fatigue Twin Registry promises to be an important resource for research on CFS and chronic fatigue.

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.

The University of Washington Twin Registry is a community-based registry of twins identified from the Washington State Department of Licensing. A fortuitous quirk in the Washington State drivers' license and identification number assignment, and collaborative Washington State laws, permitted us to build a statewide registry. Since obtaining approval from the Washington State Attorney General, the Washington State Department of Licensing has provided us with information on over 26,000 newly licensed twins, and we continue to receive computerized records on approximately 80 new twins per week. The University of Washington Twin Registry is assembled by mailing each twin a recruitment packet that includes an information sheet, brochure, brief survey, and nominal gift. Once both members of a twin pair have completed the packet, the pair is enrolled in the registry. As of June 2006, 2287 adult twin pairs have enrolled in the registry; about one half of these are female–female pairs. Among all twins, the average age is 32 years. Based on self-report, 52% of twins are monozygotic, 42% are dizygotic, and zygosity on 6% cannot yet be determined. We also have instituted a clinical protocol for collecting additional data and DNA from all twins participating in research studies requiring an in-person visit. The registry has established policies and procedures to protect the confidentiality of twin data and guidelines for the use of the registry by investigators. Plans for the further growth of the University of Washington Twin Registry and its use are discussed.

Background. Comprehensive studies of mortality among patients with chronic fatigue (CF) and chronic fatigue syndrome (CFS) have not been published, but several sources suggest that CFS is associated with an elevated risk for suicide.

Method. Data on 1201 chronically fatigued patients followed in a university-affiliated tertiary-care clinic for up to 14 years were submitted to the Center for Disease Control and Prevention (CDC) National Death Index (NDI) to evaluate all-cause and suicide-caused death rates against standardized mortality rates (SMRs). We used Life Table Analysis to examine the influence of sex and diagnoses of CFS and depression.

Results. All-cause mortality in chronically fatigued patients was no higher than expected, but suicide-caused death rates were more than eight times higher than in the US general population. The significant elevation in the SMR of suicide was restricted to those who did not meet criteria for CFS [SMRCF=14·2, 95% confidence interval (CI) 5·7–29·3 versus SMRCFS=3·6, 95% CI 0·4–12·9]. Among chronically fatigued patients who did not meet CFS criteria, those with a lifetime history of major depression (MD) had higher suicide-caused death rates than among their non-depressed counterparts (SMRMD=19·1, 95% CI 7·0–41·5 versus SMRNMD=5·6, 95% CI 0·1–31·4), although the difference was not significant.

Conclusions. CFS does not appear to be associated with increased all-cause mortality or suicide rates. Clinicians, however, should carefully evaluate patients with CF for depression and suicidality.

Background. Empirical findings suggest that psychiatric illness is associated with cardiovascular disease (CVD). The purpose of this study was to compare the strength of the association of lifetime post-traumatic stress disorder (PTSD) and lifetime major depression on CVD among Northern Plains American Indians.

Method. A total of 1414 participants aged 18–57 years completed a structured interview that assessed psychiatric diagnoses, alcohol abuse/dependence, self-reported CVD, and traditional CVD risk factors including age, sex, education, diabetes, high blood pressure, and smoking. Logistic regression analyses compared the odds ratios of CVD in participants with and without diagnosed PTSD or major depression.

Results. The rates of lifetime PTSD and major depression were 15% and 8% respectively. CVD was more commonly reported by participants with PTSD than by those without PTSD (12% v. 5%, p[les ]0·01). Likewise, more participants with major depression reported CVD than did their non-depressed counterparts (14% v. 6%, p[les ]0·05). PTSD was significantly associated with CVD even after controlling for traditional CVD risk factors and major depression (odds ratio 2·0, confidence interval 1·1–3·8). In contrast, the association of major depression with CVD was not significant after accounting for both traditional risk factors and PTSD.

Conclusions. Rates of PTSD are high in American Indian communities. Rising CVD rates in this population may be better understood if PTSD is considered along with other traditional risk factors. Future research should examine the association and mechanisms of PTSD and CVD prospectively. Such data could lead to more effective CVD prevention efforts for American Indians.