Cap Analysis of Gene Expression Clarifies Transcriptomic Divergence Within Monozygotic Twin Pairs.

Phenotypic variation is the result of gene expression based on complex interaction between genetic and environmental factors. It is well known that genetic and environmental factors influence gene expression, but our understanding of their relative importance remains limited. To obtain a hint for the understanding of their contributions, we took advantage of monozygotic twins, as they share genetic and shared environmental factors but differ in nonshared factors, such as environmental differences and stochastic factors. In this study, we performed cap analysis of gene expression on three pairs of twins and clustered each individual based on their expression profiles of annotated genes. The dendrogram of annotated gene transcripts showed a monophyletic clade for each twin pair. We also analyzed the expression of retrotransposons, such as human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), given their abundance in the genome. Clustering analyses demonstrated that HERV and LINE expression diverged even within monozygotic twin pairs. Thus, HERVs and LINEs are more susceptible to nonshared factors than annotated genes. Motif analysis of differentially expressed annotated genes suggests that specificity protein/Krüppel-like factor family transcription factors are involved in the expression divergence of annotated gene influenced by nonshared factors. Collectively, our findings suggest that expressions of annotated genes and retrotransposons are differently regulated, and that the expression of retrotransposons is more susceptible to nonshared factors than annotated genes.

Lobular Difference in Heritability of Brain Atrophy among Elderly Japanese: A Twin Study.

Background and Objectives: Brain atrophy is related to cognitive decline. However, the heritability of brain atrophy has not been fully investigated in the Eastern Asian population. Materials and Methods: Brain imaging of 74 Japanese twins registered in the Osaka University Twin Registry was conducted with voxel-based morphometry SPM12 and was processed by individual voxel-based morphometry adjusting covariates (iVAC) toolbox. The atrophy of the measured lobes was obtained by comparing the focal volume to the average of healthy subjects. Classical twin analysis was used to measure the heritability of its z-scores. Results: The heritability of brain atrophy ranged from 0.23 to 0.97, depending upon the lobes. When adjusted to age, high heritability was reported in the frontal, frontal-temporal, and parietal lobes, but the heritability in other lobes was lower than 0.70. Conclusions: This study revealed a relatively lower heritability in brain atrophy compared to other ethnicities. This result suggests a significant environmental impact on the susceptibility of brain atrophy the Japanese. Therefore, environmental factors may have more influence on the Japanese than in other populations.

Utilizing Graphical Analysis of Chest Radiographs for Primary Screening of Osteoporosis.

Background and Objectives: Osteoporosis is a major risk of fractures, harming patients' quality of life. Dual-energy X-ray absorptiometry (DXA), which can detect osteoporosis early, is too expensive to be conducted on a regular basis. Therefore, we aimed to evaluate a screening method using chest radiographs developed in Japan applied to another population. Materials and Methods: Fifty-five patients who had a chest radiograph and DXA and applied within three months of each test were recruited from the patient database of Semmelweis University (Budapest, Hungary). Graphical analysis of the chest radiographs was conducted to identify the ratio of the cortical bone in the clavicle of each patient. Two researchers performed the analysis, and multiple regression was conducted to determine the bone mineral density of each patient provided by DXA. Results: The Pearson correlation between two examiners' determinations of the cortical bone ratio was 0.769 (p < 0.001). The multiple regression model proved to be statistically significant in identifying osteoporosis, but the model adopted for the Hungarian population was different compared to the Japanese population. Conclusions: This simple, economic Japanese graphical analysis method for chest radiographs may be feasible in detecting osteoporosis. Further studies with a larger population of patients with greater variety of ethnicity would be of value in improving the accuracy of this model.

Relationship between Nutrient Intake and Human Gut Microbiota in Monozygotic Twins.

Background and Objectives: The gut microbiota is associated with human health and dietary nutrition. Various studies have been reported in this regard, but it is difficult to clearly analyze human gut microbiota as individual differences are significant. The causes of these individual differences in intestinal microflora are genetic and/or environmental. In this study, we focused on differences between identical twins in Japan to clarify the effects of nutrients consumed on the entire gut microbiome, while excluding genetic differences. Materials and Methods: We selected healthy Japanese monozygotic twins for the study and confirmed their zygosity by matching 15 short tandem repeat loci. Their fecal samples were subjected to 16S rRNA sequencing and bioinformatics analyses to identify and compare the fluctuations in intestinal bacteria. Results: We identified 12 genera sensitive to environmental factors, and found that Lactobacillus was relatively unaffected by environmental factors. Moreover, we identified protein, fat, and some nutrient intake that can affect 12 genera, which have been identified to be more sensitive to environmental factors. Among the 12 genera, Bacteroides had a positive correlation with retinol equivalent intake (rs = 0.38), Lachnospira had a significantly negative correlation with protein, sodium, iron, vitamin D, vitamin B6, and vitamin B12 intake (rs = -0.38, -0.41, -0.39, -0.63, -0.42, -0.49, respectively), Lachnospiraceae ND3007 group had a positive correlation with fat intake (rs = 0.39), and Lachnospiraceae UCG-008 group had a negative correlation with the saturated fatty acid intake (rs = -0.45). Conclusions: Our study is the first to focus on the relationship between human gut microbiota and nutrient intake using samples from Japanese twins to exclude the effects of genetic factors. These findings will broaden our understanding of the more intuitive relationship between nutrient intake and the gut microbiota and can be a useful basis for finding useful biomarkers that contribute to human health.

Update on Osaka University Twin Registry: An Overview of Multidisciplinary Research Resources and Biobank at Osaka University Center for Twin Research.

The Osaka University Twin Registry was originally established as a registry of older twins but was subsequently expanded to include twins of all ages. The Center for Twin Research at Osaka University Graduate School of Medicine has been managing this registry, as well as collecting research information and bioresources from twin participants. Based on the resources, multidisciplinary research projects have been conducted in collaboration with researchers from institutions both inside and outside Japan. One of the main aims of the center is to collect research information as well as biological resources from registered twins, and to establish a biobank and databases of these data and bioresources. Although data availability may vary, the following data have been collected: physical data (e.g., height, body weight, blood pressure, theoretical visceral fat, pulse wave velocity and bone density); epidemiological data (e.g., medical history, lifestyle, quality of life, mood status, cognitive function and nutritional status); electrocardiography, ultrasonography (carotid artery and thyroid); dentistry, dermatological assessment; positron emission tomography; magnetoencephalographam; brain magnetic resonance imaging (MRI); and functional MRI. In addition to these in-person survey data, microbiome data have been collected from some participants. As for bioresources, peripheral blood is obtained from the participants for isolation of serum and extraction of DNA and RNA, then stored in deep freezers for further analyses. A variety of research projects are in progress and more are on the way both in Japan and internationally using these data.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

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.

Association between salivary flow rate and depressive symptoms with adjustment for genetic and family environmental factors in Japanese twin study.

OBJECTIVES: The association between salivary flow rate (SFR) and depressive symptoms have been inconclusive. The present study aimed to investigate the association between SFR and depressive symptoms with and without adjustment for genetic and family environmental factors. MATERIALS AND METHODS: We conducted a cross-sectional study using twins and measured SFR and depressive symptoms as the outcome and explanatory variables, respectively. We also performed three-step regression analyses by first analysing the association between SFR and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed between-within analyses using monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs, and finally using only MZ twin pairs. These between-within analyses estimated the coefficients adjusted for genetic and family environmental factors. Furthermore, differences in the associations between individual-level and between-within suggest confounding by genetic and family environmental factors. RESULTS: We conducted 448 twins aged ≥20 years. In individual-level analyses in males and between-within analyses using MZ and same-sex DZ male twin pairs, SFR associated with depressive symptoms. In between-within analyses using only MZ male twin pairs, SFR did not associate with depressive symptoms. In females, SFR did not associate with depressive symptoms in both individual-level and between-within analyses. CONCLUSIONS: The present study revealed that the association between SFR and depressive symptoms was affected by common genetic factors in males. CLINICAL RELEVANCE: Understanding this association between SFR and depressive symptoms with adjustment for genetic and family environmental factors could lead to an important consideration for the prevention and treatment of hyposalivation.

Language-related cerebral oscillatory changes are influenced equally by genetic and environmental factors.

Twin studies have suggested that there are genetic influences on inter-individual variation in terms of verbal abilities, and candidate genes have been identified by genome-wide association studies. However, the brain activities under genetic influence during linguistic processing remain unclear. In this study, we investigated neuromagnetic activities during a language task in a group of 28 monozygotic (MZ) and 12 dizygotic (DZ) adult twin pairs. We examined the spatio-temporal distribution of the event-related desynchronizations (ERDs) in the low gamma band (25-50Hz) using beamformer analyses and time-frequency analyses. Heritability was evaluated by comparing the respective MZ and DZ correlations. The genetic and environmental contributions were then estimated by structural equation modeling (SEM). We found that the peaks of the low gamma ERDs were localized to the left frontal area. The power of low gamma ERDs in this area exhibited higher similarity between MZ twins than that between DZ twins. SEM estimated the genetic contribution as approximately 50%. In addition, these powers were negatively correlated with the behavioral verbal scores. These results improve our understanding of how genetic and environmental factors influence cerebral activities during linguistic processes.

Association between subjective memory complaints and depressive symptoms after adjustment for genetic and family environmental factors in a Japanese twin study.

OBJECTIVES: The aim of this study was to investigate the association between subjective memory complaints (SMCs) and depressive symptoms, with and without adjustment for genetic and family environmental factors. METHODS: We conducted a cross-sectional study using twins and measured SMCs and depressive symptoms as outcomes and explanatory variables, respectively. First, we performed regression analyses using generalized estimating equations to investigate the associations between SMCs and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed regression analyses for within-pair differences using monozygotic (MZ) and dizygotic (DZ) twin pairs and MZ twin pairs to investigate these associations with adjustment for genetic and family environmental factors by subtracting the values of one twin from those of co-twin variables (within-pair level analyses). Therefore, differences between the associations at individual- and within-pair level analyses suggested confounding by genetic factors. RESULTS: We included 556 twins aged ≥ 20 years. In the individual-level analyses, SMCs were significantly associated with depressive symptoms in both males and females [standardized coefficients: males, 0.23 (95% CI 0.08-0.38); females, 0.35 (95% CI 0.23-0.46)]. In the within-pair level analyses using MZ and same-sex DZ twin pairs, SMCs were significantly associated with depressive symptoms. In the within-pair level analyses using the MZ twin pairs, SMCs were significantly associated with depressive symptoms [standardized coefficients: males, 0.32 (95% CI 0.08-0.56); females, 0.24 (95% CI 0.13-0.42)]. CONCLUSIONS: This study suggested that SMCs were significantly associated with depressive symptoms after adjustment for genetic and family environmental factors.

A longitudinal twin study on Tojikomori and depressive symptoms in Japanese elderly.

BACKGROUND: Genetic factors associated with Tojikomori (being housebound without any limitations in physical functioning or mental problems) are unclear. We performed a twin study to help clarify the causes of Tojikomori and investigate the association between Tojikomori and depressive symptoms. METHODS: Participants were members of the Osaka University Aged Twin Registry. A total of 157 twin pairs (314 individuals) who provided data in 2008 and 2012 were included. Depressive symptoms were measured by the Geriatric Depression Scale short version (GDS). Social Activities Scores (SAS) were measured with questions assessing the frequency of going out and contact with others. Activities of daily living were assessed with the Barthel index. Structural equation modelling analysis was used to evaluate the relative importance of genes and environments for the phenotypes measured. RESULTS: In the first analysis, for SAS (2012), 25% of the variance was explained by additive genetic effects, and 75% was explained by unique environmental (including error) effects. For the GDS (2012), 28% of the variance was explained by additive genetic effects, and 72% was explained by unique environmental (including error) effects. In the second analysis, 25% of the total variance in SAS (2012) was explained by additive genetic factors, which influenced GDS scores (2008 and 2012). However, only 10% of the total variance in GDS scores (2012) was explained by additive genetic factors that influenced SAS (2008 and 2012). CONCLUSIONS: Tojikomori was influenced by genetic factors in the elderly Japanese subjects. The association between Tojikomori and depressive symptoms was explained by genetic and environmental factors that are common to both phenotypes. Depressive symptoms were a cause of future Tojikomori and were affected by additive genetic factors. Genetic factors of Tojikomori were not a major cause of future depressive symptoms.

Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project.

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.

The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits.

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 relationship between body mass index and uric acid: a study on Japanese adult twins.

OBJECTIVES: The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors. METHODS: The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow's Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed. RESULTS: In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0.194 (95 % confidence interval: 0.016-0.373) in men and 0.186 (95 % confidence interval: 0.071-0.302) in women. Considering twin-pair difference value analyses, standardized regression coefficients were 0.333 (95 % confidence interval: 0.072-0.594) in men and 0.314 (95 % confidence interval: 0.151-0.477) in women. CONCLUSIONS: The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.

Common genetic factors influence hand strength, processing speed, and working memory.

BACKGROUND: It is important to detect cognitive decline at an early stage, especially before onset of mild cognitive impairment and dementia. Processing speed and working memory are aspects of cognitive function that are associated with cognitive decline. Hand strength is an inexpensive, easily measurable indicator of cognitive decline. However, associations between hand strength, processing speed, and working memory have not been studied. In addition, the genetic and environmental structure of the association between hand strength and cognitive decline is unclear. We investigated phenotypic associations between hand strength, processing speed, and working memory and examined the genetic and environmental structure of the associations between phenotypes. METHODS: Hand strength, processing speed (digit symbol performance), and working memory (digit span performance) were examined in monozygotic and dizygotic twin pairs. Generalized estimating equations were used to identify phenotypic associations, and structural equation modeling was used to investigate the genetic and environmental structure of the association. RESULTS: Generalized estimating equations showed that hand strength was phenotypically associated with digit symbol performance but not with digit span performance. Structural equation modeling showed that common genetic factors influenced hand strength and digit symbol and digit span performance. CONCLUSIONS: There was a phenotypic association between hand strength and processing speed. In addition, some genetic factors were common to hand strength, processing speed, and working memory.

Foreign Patients Visiting the Emergency Department: A Systematic Review of Studies in Japan.

Background: As the number of non-native patients in Japan is increasing, emergency departments must provide proper care for international patients. However, no research has been conducted to determine the demographics of international patients that visit Japanese hospitals or the requirements to accept them. We aimed to organize the existing research and its patterns for foreign patients in Japan's emergency departments and to identify the areas that require further research. Methods: Systematic review of research articles indexed in MEDLINE and Ichushi-web (Japanese medical literature) was conducted. The search strategy was based on a previous study in Japanese, and the search was limited to manuscripts published from 2015. Results: Nine publications that reported on the demographic characteristics of foreign patients who visited the emergency department were among the study's 13 references. Injury diagnoses and the Asian population were both common. Dealing with overseas patients can be challenging due to linguistic barriers, cultural differences, and payment issues. However, studies describing the spoken language and the type of healthcare insurance used were lacking. Furthermore, neither the definition of "foreign patients" nor the distinction between short-term visitors and long-term residents were made in the majority of the research. Conclusions: The demographic characteristics of patients differed depending on the location and facility, despite the fact that several characteristics of foreign patients in emergency departments appeared to be generalizable. The COVID-19 pandemic may modify the demographic characteristics of immigrants; thus, more research from a broad range of locations and medical facilities is still necessary.

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

A simple method for in planta tomato transformation by inoculating floral buds with a sticky Agrobacterium tumefaciens suspension.

Tomato transformation is conventionally performed using Agrobacterium tumefaciens-infected cotyledons. Here, we propose a simple procedure for tomato transformation, by which A. tumefaciens cells were smeared onto floral buds of a tomato plant using a paintbrush. Sufficient numbers of fruits were obtained from them, although the smearing of an excess number of A. tumefaciens cells led to an adverse effect on the plant growth. Progeny plants were screened by growth on a kanamycin-containing selection medium plate. The nptII gene was detected in 10 plants among 1,599 progenies. These transformants were derived from fruits other than those obtained from the smeared buds. This suggested that A. tumefaciens cells moved to the buds located near the smeared buds and caused the transformation event. Our findings suggest that this procedure can be used for the introduction of a foreign gene into plant cells.

Model Comparisons of the Cost Effectiveness of Rubella Vaccination Method in Japanese Adults.

The number of rubella cases has increased in Japan, especially among adults. Rubella infection in pregnant females can lead to congenital rubella syndrome (CRS). The Japanese government is promoting vaccination to prevent CRS. This study performs a cost-effectiveness analysis of the following four methods: (1) females who wished to become pregnant and partners, with an antibody-titer test; (2) females only, with an antibody-titer test; (3) females and males, without an antibody-titer test; (4) females only, without an antibody-titer test. A decision tree model with a hypothetical cohort of 500 males and 500 females was used for the analysis, and the parameters were obtained from previous studies. The number of avoidances of CRS was defined as the effect. Compared to the case where methods were not implemented, the number of CRS cases that can be prevented by implementing the methods was 0.0115589 by (1) and (3) and 0.0147891 by (2) and (4). The cost effectiveness of (1) to (4) was 287,413,677 JPY, 135,050,529 JPY, 388,524,974 JPY, and 197,744,219 JPY, respectively (1 JPY = 0.00963247 USD). Method (2) was the most cost-effective and did not change by sensitivity analysis. We conclude that the vaccination for females only with an antibody-titer test is recommended.

Heritability and Environmental Correlation of Phase Angle with Anthropometric Measurements: A Twin Study.

Bioelectrical impedance analysis (BIA)-derived phase angle (PhA) is a valuable parameter to assess physical health. However, the genetic and environmental aspects of PhA are not yet well understood. The present study aimed to estimate the heritability of PhA and investigate the relationships between PhA and anthropometric measurements. PhA and skeletal muscle mass index (SMI) were examined using multi-frequency BIA in 168 Japanese twin volunteers (54 males and 114 females; mean age = 61.0 ± 16.5 years). We estimated the narrow-sense heritability of these parameters and the genetic and environmental relationships between them using a genetic twin modeling. For the PhA, 51% (95% confidence interval: 0.33, 0.64) of the variance was explained by additive genetic effects, and 49% (95% confidence interval: 0.36, 0.67) was explained by unique environmental effects. The heritability of PhA was lower than the height, body weight, and body mass index. PhA shared almost no genetic variation with anthropometric measurements and SMI but shared an environmental variation (14%) with SMI. These findings suggest that the genes affecting PhA are different than those affecting anthropometric measurements and SMI. The correlation between PhA and SMI is caused by common environmental factors.

Survey of satisfaction regarding palliative care provided to patients who died at home or in a hospital.

BACKGROUND: Improvement in quality of life (QoL) of patients is one of the most important goals of palliative care, but evaluation of QoL of patients is difficult. AIM: To evaluate QoL of patients who died at home or in a hospital. METHODS: We administered the Good Death Inventory (10 core and 8 optional domains) to the bereaved families of patients who died at home or in a hospital. A total of 107 bereaved families undertook a survey. FINDINGS: If a bereaved family chose 'somewhat agree', 'agree' or 'absolutely agree', the answer was regarded as a 'satisfactory answer'. Regarding the 10 core domains, of patients who died in a hospital, <50% respondents gave a 'satisfactory answer' to three questions, whereas of patients who died at home, >60% of respondents gave a 'satisfactory answer' to seven questions. Regarding the eight optional domains, of patients who died in a hospital, <50% respondents gave a 'satisfactory answer' to five questions, whereas of patients who died at home, >60% of respondents gave a 'satisfactory answer' to four questions. CONCLUSIONS: QoL of patients who died at home appeared higher than that of those who died in a hospital. Patients prefer to remain at home rather than in a hospital, probably because at home they are surrounded by familiar things and can live according to their usual habits.