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Aim: Genome-wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD-associated loci., Methods: The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping. Of them, 1421, 1264, and 225 were classified as PPD based on the Edinburgh Postnatal Depression Scale 1 month after delivery. The most influential confounding factors of genetic liability to PPD were selected, and logistic regression analyses were performed to evaluate genetic associations with PPD after adjusting for confounders., Results: A meta-analysis of GWAS results from the three cohorts identified significant associations between PPD and the following loci (P < 5 × 10 -8 ) by integrating the number of deliveries and the number of family members living together as the most influential confounders: rs377546683 at DAB1, rs11940752 near UGT8, rs141172317, rs117928019, rs76631412, rs118131805 at DOCK2, rs188907279 near ZNF572, rs504378, rs690150, rs491868, rs689917, rs474978, rs690118, rs690253 near DIRAS2, rs1435984417 at ZNF618, rs57705782 near PTPRM, and rs185293917 near PDGFB. Pathway analyses indicated that SNPs suggestively associated with PPD were mostly over-represented in categories including long-term depression, GnRH signaling, glutamatergic synapse, oxytocin signaling, and Rap1 signaling., Conclusion: The current GWAS study identified eight loci significantly associated with PPD, which may clarify the genetic structure underlying its pathogenesis., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: We aim to discover which, if any, of the subscales of internalizing and externalizing behavioral problems at age 3 are still associated with screen time (ST) at age 2 after adjusting for behavioral problems scores at age 2., Methods: This study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Information was gathered prospectively, with 7207 mother-child pairs included in the analysis. Children's ST was categorized in hours a day at age 2 (<1, 1-<2, 2-<4, ≥4). We assessed children's behavioral problems using the Child Behavior Checklist for Ages 1½-5 (CBCL) at ages 2 and 3. 'Having behavioral problems' was defined by them being within a clinical range for internalizing behaviors (withdrawn, somatic complaints, anxious/depressed and emotionally reactive) and externalizing behaviors (attention problems and aggressive behaviors) at age 3. Continuous scores on each of the behavioral problem scales at age 2 were used as covariates., Results: Greater ST for children at age 2 was associated with specific subscales for emotionally reactive and aggressive behaviors at age 3., Conclusions: This study found that ST is prospectively associated with some behavioral scales but not others., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey., Methods: The second period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the second period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The second period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC)., Results: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the second period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the second period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits., Conclusion: The second period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Few population-based studies including younger adults have examined the potential of olfactory function tests to capture the degree of atrophy in memory-associated brain regions, which cannot be adequately explained by cognitive function tests screening for cognitive impairment. This population-based study investigated associations between high-resolution olfactory test data with few odours and grey matter volumes (GMVs) of the left and right hippocampi, amygdala, parahippocampi, and olfactory cortex, while accounting for differences in cognitive decline, in 1444 participants (aged 31-91 years). Regression analyses included intracranial volume (ICV)-normalised GMVs of eight memory-related regions as objective variables and age, sex, education duration, smoking history, olfaction test score, and the Montreal Cognitive Assessment-Japanese version (MoCA-J) score as explanatory variables. Significant relationships were found between olfactory test scores and ICV-normalised GMVs of the left and right hippocampi and left amygdala (p = 0.020, 0.024, and 0.028, respectively), adjusting for the MoCA-J score. The olfactory test score was significantly related to the right amygdalar GMV (p = 0.020) in older adults (age ≥ 65 years). These associations remained significant after applying Benjamini-Hochberg multiple testing correction (false discovery rate < 0.1). Therefore, olfactory and cognitive function tests may efficiently capture the degree of atrophy in the hippocampi and amygdala, especially in older adults., (© 2024. The Author(s).)

Introduction: The Tohoku Medical Megabank (TMM) was established for creative reconstruction from the Great East Japan Earthquake and tsunami in 2011. Two prospective genome cohort studies in Miyagi prefecture have successfully recruited approximately 127,000 participants. The health status of these individuals was evaluated at the initial recruitment, and follow-up health checkups have been conducted every 5 years. During these health checkups, unexpected critical values were encountered, which prompted us to develop an urgent notification system., Methods: We analyzed the frequency of critical values observed in home blood pressure (HBP) test in an urgent notification office (UNO). We returned the critical values by urgent notification before the notifications of regular results. In addition, the impact of the TMM urgent notification on the participants was evaluated., Results: We issued urgent notifications of the critical values of extremely high HBP. Of the 21,061 participants who underwent HBP measurements, 256 (1.2%) met the criteria for urgent notification. It was found that abnormalities in blood sugar levels, renal function, and lipid values were frequently concurrent with the abnormal HBP readings. Annual questionnaires administered after the urgent notification, approximately 60% of those went to hospitals or clinics., Conclusions: The urgent notification system for hypertensive emergency with HBP in the TMM was well accepted by the participants and encouraged them to seek medical care. The system has been useful in addressing the prolonged healthcare problems and in promoting health care in large-scale disaster damaged areas., Competing Interests: None, (Copyright © Japan Medical Association.)

Introduction: To examine the interaction between lifestyle habits and the COVID-19 vaccinations for preventing SARS-CoV-2 infection, we analyzed 11,016 adult participants registered in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study., Methods: Lifestyle variables, including regular exercise, smoking and drinking habits, sleep status, body mass index, and daily breakfast consumption, were assessed from 2014 to 2019 using baseline questionnaires. Information on SARS-CoV-2 infection and the COVID-19 vaccination were also collected from March 2020 to May 2023. The study period was divided into two in the postvaccination phase: the first period (the beginning of the vaccination program) and the second period (the fourth shot onward)., Results: In the Cox proportional-hazards model analysis, the five-time vaccinations group showed a significantly lower risk of SARS-CoV-2 infection adjusted age, sex, underlying health condition, and lifestyle variables (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.76-0.86). Logistic regression analysis revealed that a higher number of vaccinations was significantly associated with a low risk of SARS-CoV-2 infection regardless of lifestyle habits (three times in the first period: odds ratio [OR] 0.19, 95% CI 0.15-0.24; five times in the second period: OR 0.07, 95% CI 0.05-0.11 vs. none). Regarding lifestyle habits, the risk reduction in those who had sleep satisfaction (OR 0.12, 95% CI 0.08-0.18) was slightly larger than in those who had sleep dissatisfaction (OR 0.23, 95% CI 0.17-0.32) in the group with the highest number of vaccinations in the first period; however, this interaction was hardly confirmed in the second period when the number of infected cases significantly increased., Conclusions: Our findings indicated that a higher number of COVID-19 vaccinations was associated with reduced risk of SARS-CoV-2 infection; otherwise, we may need to understand the advantages and limitations of a healthy lifestyle for preventing infection depending on the situation with vaccinations and infection spreading., Competing Interests: None, (Copyright © Japan Medical Association.)

Genetic testing is key in modern healthcare, particularly for monogenic disorders such as familial hypercholesterolemia. This Tohoku Medical Megabank Project study explored the impact of first-degree relatives' dyslipidemia history on individual responses to familial hypercholesterolemia genomic results. Involving 214 participants and using Japan's 3.5KJPN genome reference panel, the study assessed preferences and intentions regarding familial hypercholesterolemia genetic testing results. The data revealed a significant inclination among participants with a family history of dyslipidemia to share their genetic test results, with more than 80% of participants intending to share positive results with their partners and children and 98.1% acknowledging the usefulness of positive results for personal health management. The study underscores the importance of family health history in genetic-testing perceptions, highlighting the need for family-centered approaches in genetic counseling and healthcare. Notable study limitations include the regional scope and reliance on questionnaire data. The study results emphasize the association between family health history and genetic-testing attitudes and decisions.

Genome-wide association studies have been employed to develop numerous risk prediction models using polygenic risk scores (PRSs) for multifactorial diseases. However, healthcare providers lack confidence in their understanding of PRS risk stratification for multifactorial diseases, which underscores the need to assess the readiness of PRSs for clinical use. To address this issue, we surveyed the perceptions of healthcare providers as stakeholders in the clinical implementation of genetic-based risk prediction for multifactorial diseases. We conducted a web-based study on the need for risk prediction based on genetic information and the appropriate timing of testing for 12 multifactorial diseases. Responses were obtained from 506 stakeholders. Positive perceptions of genetic risk testing were found for adult-onset chronic diseases. As per participant opinion, testing for adult-onset diseases should be performed after the age of 20 years, whereas testing for psychiatric and allergic disorders that manifest during childhood should be performed from birth to 19 years of age. The stakeholders recognized the need for genetic risk testing for diseases that develop in adulthood, believing that the appropriate testing time is after maturity. This study contributes to the discussion on the clinical implementation of the PRS for genetic risk prediction of multifactorial diseases.

The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study (TMM Brain MRI Study) was established to collect multimodal information through neuroimaging and neuropsychological assessments to evaluate the cognitive function and mental health of residents who experienced the Great East Japan Earthquake (GEJE) and associated tsunami. The study also aimed to promote advances in personalized healthcare and medicine related to mental health and cognitive function among the general population. We recruited participants for the first (baseline) survey starting in July 2014, enrolling individuals who were participating in either the TMM Community-Based Cohort Study (TMM CommCohort Study) or the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). We collected multiple magnetic resonance imaging (MRI) sequences, including 3D T1-weighted sequences, magnetic resonance angiography (MRA), diffusion tensor imaging (DTI), pseudo-continuous arterial spin labeling (pCASL), and three-dimensional fluid-attenuated inversion recovery (FLAIR) sequences. To assess neuropsychological status, we used both questionnaire- and interview-based rating scales. The former assessments included the Tri-axial Coping Scale, Impact of Event Scale in Japanese, Profile of Mood States, and 15-item Depression, Anxiety, and Stress Scale, whereas the latter assessments included the Mini-Mental State Examination, Japanese version. A total of 12,164 individuals were recruited for the first (baseline) survey, including those unable to complete all assessments. In parallel, we returned the MRI results to the participants and subsequently shared the MRI data through the TMM Biobank. At present, the second (first follow-up) survey of the study started in October 2019 is underway. In this study, we established a large and comprehensive database that included robust neuroimaging data as well as psychological and cognitive assessment data. In combination with genomic and omics data already contained in the TMM Biobank database, these data could provide new insights into the relationships of pathological processes with neuropsychological disorders, including age-related cognitive impairment., Competing Interests: None, (Copyright © Japan Medical Association.)

Introduction: Perinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV)., Methods: Nine HRV indicators (features) and sleep-wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep-wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated-shallow sleep, deep sleep, and the two types of wake conditions-was also tested., Results and Discussion: In the test for predicting three types of sleep-wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82-0.88) and accuracy (0.78-0.81). The test using four types of sleep-wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep-wake conditions. Among the seven features, "the number of interval differences of successive RR intervals greater than 50 ms (NN50)" and "the proportion dividing NN50 by the total number of RR intervals (pNN50)" were useful to predict sleep-wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Ono, Warita, Shoji, Nakagawa, Usukura, Yu, Takahashi, Ichiji, Sugita, Kobayashi, Kikuchi, Kimura, Hamaie, Hino, Kunii, Murakami, Ishikuro, Obara, Nakamura, Nagami, Takai, Ogishima, Sugawara, Hoshiai, Saito, Tamiya, Fuse, Fujii, Nakayama, Kuriyama, Yamamoto, Yaegashi, Homma and Tomita.)

Background: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy., Aims: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy., Methods: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays., Results: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients., Conclusions: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children's Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.

Background: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment., Objective: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association., Methods: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021., Results: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024)., Conclusions: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

Background: Recent advances in human genome research have provided evidence for genotype-phenotype associations, pathogenicity, and clinical actionability of variants and genomic risk prediction of disease. However, the return of individual genomic results to healthy individuals is fraught with ethical and practical complexity., Methods: Individual genomic results were returned to BRCA1/2 pathogenic variant (PV) carriers of the Tohoku Medical Megabank cohort study participants with an information on hereditary breast and ovarian cancer syndrome (HBOC). One hundred and eighty participants, including 9 BRCA1/2 PV carriers, were asked about their willingness to receive individual genomic results, without revealing the gene name and related disorders, prior to the study. Of the 142 participants who responded, 103 showed willingness to know their genomic information. Each of the six BRCA1/2 PV carriers who consented to participate in the study received information about HBOC in person and underwent validation testing with blood resampling., Results: All participants were in their 60s or 70s; of the four females and two males, two had a history of breast cancer and five had a family history of HBOC-related cancers. All participants appreciated the information, without remarkable negative psychological impact of the return, and intended to undergo clinical risk surveillance. Five participants were accompanied by family members while receiving the results, and three first-degree female relatives wished to undergo genomic testing at the hospital., Conclusions: Our results suggest that returning actionable genomic information to participants in a population-based genome cohort study is beneficial for preventing or providing early-stage intervention for associated diseases., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases., (© 2022. The Author(s).)

Introduction: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings., Methods: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1 , CYP2C19 , and NUDT15 , were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study., Results: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable., Conclusions: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting., Competing Interests: None, (Copyright © Japan Medical Association.)

In this study, the extent to which different emotions of pregnant women can be predicted based on heart rate-relevant information as indicators of autonomic nervous system functioning was explored using various machine learning algorithms. Nine heart rate-relevant autonomic system indicators, including the coefficient of variation R-R interval (CVRR), standard deviation of all NN intervals (SDNN), and square root of the mean squared differences of successive NN intervals (RMSSD), were measured using a heart rate monitor (MyBeat) and four different emotions including "happy," as a positive emotion and "anxiety," "sad," "frustrated," as negative emotions were self-recorded on a smartphone application, during 1 week starting from 23rd to 32nd weeks of pregnancy from 85 pregnant women. The k-nearest neighbor (k-NN), support vector machine (SVM), logistic regression (LR), random forest (RF), naïve bayes (NB), decision tree (DT), gradient boosting trees (GBT), stochastic gradient descent (SGD), extreme gradient boosting (XGBoost), and artificial neural network (ANN) machine learning methods were applied to predict the four different emotions based on the heart rate-relevant information. To predict four different emotions, RF also showed a modest area under the receiver operating characteristic curve (AUC-ROC) of 0.70. CVRR, RMSSD, SDNN, high frequency (HF), and low frequency (LF) mostly contributed to the predictions. GBT displayed the second highest AUC (0.69). Comprehensive analyses revealed the benefits of the prediction accuracy of the RF and GBT methods and were beneficial to establish models to predict emotions based on autonomic nervous system indicators. The results implicated SDNN, RMSSD, CVRR, LF, and HF as important parameters for the predictions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ono, Warita, Shoji, Nakagawa, Usukura, Yu, Takahashi, Ichiji, Sugita, Kobayashi, Kikuchi, Kunii, Murakami, Ishikuro, Obara, Nakamura, Nagami, Takai, Ogishima, Sugawara, Hoshiai, Saito, Tamiya, Fuse, Kuriyama, Yamamoto, Yaegashi, Homma and Tomita.)

Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data., Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs)., Participants: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined., Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10 -8 ) in each stage of the study and in the subsequent meta-analysis., Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages., Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance ( P < 5 × 10 -8 ). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci., Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL., (© 2022 by the American Academy of Ophthalmology.)

Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational "genetics workshop" on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

To reveal gene-environment interactions underlying common diseases and estimate the risk for common diseases, the Tohoku Medical Megabank (TMM) project has conducted prospective cohort studies and genomic and multiomics analyses. To establish an integrated biobank, we developed an integrated database called "dbTMM" that incorporates both the individual cohort/clinical data and the genome/multiomics data of 157,191 participants in the Tohoku Medical Megabank project. To our knowledge, dbTMM is the first database to store individual whole-genome data on a variant-by-variant basis as well as cohort/clinical data for over one hundred thousand participants in a prospective cohort study. dbTMM enables us to stratify our cohort by both genome-wide genetic factors and environmental factors, and it provides a research and development platform that enables prospective analysis of large-scale data from genome cohorts., (© 2021. The Author(s).)

Background: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases., Methods: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely., Results: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex., Conclusion: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

The accuracy of previous genetic studies in predicting polygenic psychiatric phenotypes has been limited mainly due to the limited power in distinguishing truly susceptible variants from null variants and the resulting overfitting. A novel prediction algorithm, Smooth-Threshold Multivariate Genetic Prediction (STMGP), was applied to improve the genome-based prediction of psychiatric phenotypes by decreasing overfitting through selecting variants and building a penalized regression model. Prediction models were trained using a cohort of 3685 subjects in Miyagi prefecture and validated with an independently recruited cohort of 3048 subjects in Iwate prefecture in Japan. Genotyping was performed using HumanOmniExpressExome BeadChip Arrays. We used the target phenotype of depressive symptoms and simulated phenotypes with varying complexity and various effect-size distributions of risk alleles. The prediction accuracy and the degree of overfitting of STMGP were compared with those of state-of-the-art models (polygenic risk scores, genomic best linear-unbiased prediction, summary-data-based best linear-unbiased prediction, BayesR, and ridge regression). In the prediction of depressive symptoms, compared with the other models, STMGP showed the highest prediction accuracy with the lowest degree of overfitting, although there was no significant difference in prediction accuracy. Simulation studies suggested that STMGP has a better prediction accuracy for moderately polygenic phenotypes. Our investigations suggest the potential usefulness of STMGP for predicting polygenic psychiatric conditions while avoiding overfitting.

In order to assess the long-term impact of the Great East Japan Earthquake on the oral health of disaster victims and to evaluate gene-environmental interactions in the development of major oral diseases and oral-systemic associations, the oral part of two large-scale genome cohort studies by the Tohoku Medical Megabank Organization (ToMMo), including the Community-based cohort (CommCohort) study and the Birth and Three-Generation cohort (BirThree) study, have been conducted. The study population comprised 32,185 subjects, including 16,886 participants in the CommCohort study and 15,299 participants in the BirThree cohort study, recruited from 2013 to 2017. The oral studies consist of a questionnaire regarding oral hygiene behavior, clinical examinations by dentists, and oral plaque and saliva sampling for microbiome analyses, which were carried out at seven community support centers in Miyagi prefecture. The median age of all participants was 55.0 years, and 66.1% of participants were women. Almost all participants reported that they brushed their teeth more than once a day. The median number of present teeth was 27.0, and the decayed, missing and filled tooth number was 16.0, with a significant difference according to age and sex. The median periodontal pocket and clinical attachment level was 2.48 mm and 4.00 mm, respectively. Periodontal parameters increased significantly according to age, except for the accumulation of dental calculus. The oral part of these extensive cross-sectional studies provides a unique and important platform for future studies on oral health and diseases that elicit through interactions with systemic diseases, lifestyles, life events and genetic backgrounds, and contributes to researches clarifying the long-term effects of disasters on oral health.

To solve major limitations in algorithms for the metabolite-based prediction of psychiatric phenotypes, a novel prediction model for depressive symptoms based on nonlinear feature selection machine learning, the Hilbert-Schmidt independence criterion least absolute shrinkage and selection operator (HSIC Lasso) algorithm, was developed and applied to a metabolomic dataset with the largest sample size to date. In total, 897 population-based subjects were recruited from the communities affected by the Great East Japan Earthquake; 306 metabolite features (37 metabolites identified by nuclear magnetic resonance measurements and 269 characterized metabolites based on the intensities from mass spectrometry) were utilized to build prediction models for depressive symptoms as evaluated by the Center for Epidemiologic Studies-Depression Scale (CES-D). The nested fivefold cross-validation was used for developing and evaluating the prediction models. The HSIC Lasso-based prediction model showed better predictive power than the other prediction models, including Lasso, support vector machine, partial least squares, random forest, and neural network. L-leucine, 3-hydroxyisobutyrate, and gamma-linolenyl carnitine frequently contributed to the prediction. We have demonstrated that the HSIC Lasso-based prediction model integrating nonlinear feature selection showed improved predictive power for depressive symptoms based on metabolome data as well as on risk metabolites based on nonlinear statistics in the Japanese population. Further studies should use HSIC Lasso-based prediction models with different ethnicities to investigate the generality of each risk metabolite for predicting depressive symptoms.

The Tohoku Medical Megabank Project was designed as part of the national reconstruction project for addressing the damage from the 2011 Great East Japan Earthquake. It is an integrated project involving the genome cohort study of 150,000 participants, integrated biobank construction, and multi-omics analyses. Public relations and communication activities emerged to be extremely important in the successful development of this project. To gain insights into the contributions of these activities, we divided the public relations and communication activities for the project into three phases based on the situations surrounding the project. Prior to the start of the cohort study (Phase I), a cooperative relationship was established with a focus on concluding cooperation agreements with local governments. Until the participants reached the target number (Phase II), we actively communicated with the media to publicize the project. During the phase in which use of the constructed biobank is promoted (Phase III), for ensuring the industrial utilization of the biobank, visits from the industry are promoted. Throughout the execution of these activities, we explored the best strategies for building relationships with multiple stakeholders like local government, media and industry. By paying attention to these phases that have been changing according to the project's progress, we were able to adapt the strategies and methods of public relations and communication. The success of these activities has enabled the overall project to progress smoothly. We hope that the process of designing our project's public relations and communication activities will be useful for other similar initiatives.

Large-scale, low-cost genome analysis has become possible with next-generation sequencing technology, which is currently used in research and clinical practice. Many attempts of returning individual genomic results have commenced not only in clinical practice, but also in research settings of several countries. In Japan, the government guidelines include a section on the disclosure of genetic information regarding genome analysis in research. However, no practical guidance for the return of individual genomic results in research settings (ROGRR) currently exists. We propose practical guidance regarding ROGRR in Japan based on extensive research, including a literature review of related previous studies, an examination of the relevant legislation in Japan, and interviews with stakeholders. The guidance we developed consists of "Points to consider" and "Issues for further discussion and consideration." The "Points to consider" were divided into five parts, from preliminary review before discussion of policy, to the actual return and follow-up process, in the order of the assumed ROGRR process. It is anticipated that a situation will arise where numerous research projects will consider ROGRR carefully and realistically in the future, and in the process of drafting such practical guidance, various issues requiring continuous discussion will emerge. The necessities of continuous discussion concerning ROGRR in Japan's context is increasing, particularly in terms of the ethical, legal, and social implications. We believe such discussions and considerations may contribute to creating a new system that will increase availability of personalized medicine and prevention using genetic information, allowing them to become useful to the broader population.

Objective: We aimed to investigate the association between types of housing and allergic symptoms at 3-4 years following the Great East Japan Earthquake., Methods: Our study was based on the ToMMo Child Health Study conducted in 2014 and 2015, a cross-sectional survey of public school children in Miyagi Prefecture, Japan. Of the 46 648 invited schoolchildren in the 2nd to 8th grades, 9884 were included. Presence of eczema, wheezing, and mental health symptoms was defined with questionnaires. To calculate odds ratios (ORs) and 95% CIs for the associations between types of housing and eczema or respiratory symptoms, we fitted generalized linear mixed models, included a random effect for municipality of residence, and adjusted for sex, school grade, survey year, and mental health symptoms., Results: Prefabricated temporary housing was significantly associated with eczema symptoms (OR, 1.46; 95% CI, 1.06-2.02). Even after adjusting for the presence of mental health symptoms, our analysis produced similar results (OR, 1.42; 95% CI, 1.03-1.96). Conversely, it was not significantly associated with respiratory symptoms (OR, 0.97; 95% CI, 0.61-1.54)., Conclusions: Children living in prefabricated temporary housing had a higher prevalence of eczema symptoms; however, prevalence of respiratory symptoms was not significantly higher.

The Tohoku Medical Megabank (TMM) project was established to provide creative reconstruction of the Tohoku area that suffered from a huge earthquake and ensuing tsunami (the Great East Japan Earthquake, GEJE). TMM aims to establish two large-scale genome cohorts and an integrated biobank managing biospecimen and related information. It supports community medicine by establishing next-generation medical systems through a combination of the prospective genome cohort studies with a total of 150,000 participants and genomic medicine. The strategies for genome analyses in TMM are to develop an elaborate genome reference panel by means of high-fidelity Japanese whole-genome sequence, to design custom single nucleotide polymorphism (SNP) arrays based on the reference panel, and to obtain genotype data for all the TMM cohort participants subsequently. Disease-associated genomic information and omics data, including metabolomics and microbiome analysis, provide an essential platform for precision medicine and personalized healthcare (PHC). Ethical, legal, and social issues (ELSI) and education are important for implementing genomic medicine. The major considerations of ELSI regarding each participant of the cohort studies are the respect for the autonomy and the protection of privacies. Moreover, developing and provide human resources not only for the TMM project but also for the social implementation of precision medicine and PHC is required. We started a pilot study of the return of genomic results for familial hypercholesterolemia (FH) as a target disease. TMM aims to establish solid platforms that support precision medicine and PHC based on the genomic and omics information and environmental and lifestyle factors of the individuals, which is one of the most advanced medical care beyond the evidenced-based medicine in the near future., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Genome cohort studies are used to analyze interactions between genetic and environmental factors, providing valuable information for personalized healthcare. Large-scale and long-term cohort studies require a number of specially trained personnel, of whom those involved in obtaining informed consent play a vital role, especially during the initial phase of such studies. The Japanese Society of Human Genetics (JSHG) previously established a certification system for genome medical research coordinators (GMRCs) responsible for obtaining written consent via face-to-face explanation. Meanwhile, in the Tohoku Medical Megabank Organization (ToMMo), GMRCs are expected to play important roles not only in obtaining informed consent and conducting various assessments, but also in communicating with participants throughout the long-term follow-up. Based on the JSHG program, we therefore developed a specific education and training program for ToMMo GMRCs consisting of 17 lectures, one practical training session on the informed consent procedure, and written and interview examinations. Re-education workshops aimed at self-improvement are also carried out following certification. In this study, we evaluated the education and training program in terms of overall understanding, usefulness, and satisfaction using an anonymous questionnaire., Methods: An anonymous questionnaire addressing each aspect of the education and training program (understanding, usefulness, and satisfaction) was distributed among 152 qualified ToMMo GMRCs. Responses were received from 94 participants (61.8%)., Results: There was a significant association between the level of overall understanding of lectures and medical qualification (nurse or clinical laboratory technologist), but not with age or educational background. The level of understanding and overall usefulness were lower in sessions related to genetics and epidemiology than those dealing with ToMMo practices. In the re-education workshops, GMRCs showed a preference for and hoped to learn more about both background knowledge and research progress in the ToMMo., Conclusions: The results of our questionnaire suggest that not all ToMMo GMRCs are able to understand everything during the initial education and training program, especially in terms of genomic medicine. Continuous re-education is therefore vital in improving knowledge, skills and motivation, and preparing GMRCs for a specialist role in community-based personalized healthcare.

In recent genome analyses, population-specific reference panels have indicated important. However, reference panels based on short-read sequencing data do not sufficiently cover long insertions. Therefore, the nature of long insertions has not been well documented. Here, we assembled a Japanese genome using single-molecule real-time sequencing data and characterized insertions found in the assembled genome. We identified 3691 insertions ranging from 100 bps to ~10,000 bps in the assembled genome relative to the international reference sequence (GRCh38). To validate and characterize these insertions, we mapped short-reads from 1070 Japanese individuals and 728 individuals from eight other populations to insertions integrated into GRCh38. With this result, we constructed JRGv1 (Japanese Reference Genome version 1) by integrating the 903 verified insertions, totaling 1,086,173 bases, shared by at least two Japanese individuals into GRCh38. We also constructed decoyJRGv1 by concatenating 3559 verified insertions, totaling 2,536,870 bases, shared by at least two Japanese individuals or by six other assemblies. This assembly improved the alignment ratio by 0.4% on average. These results demonstrate the importance of refining the reference assembly and creating a population-specific reference genome. JRGv1 and decoyJRGv1 are available at the JRG website., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

Personalized healthcare (PHC) based on an individual's genetic make-up is one of the most advanced, yet feasible, forms of medical care. The Tohoku Medical Megabank (TMM) Project aims to combine population genomics, medical genetics and prospective cohort studies to develop a critical infrastructure for the establishment of PHC. To date, a TMM CommCohort (adult general population) and a TMM BirThree Cohort (birth+three-generation families) have conducted recruitments and baseline surveys. Genome analyses as part of the TMM Project will aid in the development of a high-fidelity whole-genome Japanese reference panel, in designing custom single-nucleotide polymorphism (SNP) arrays specific to Japanese, and in estimation of the biological significance of genetic variations through linked investigations of the cohorts. Whole-genome sequencing from >3,500 unrelated Japanese and establishment of a Japanese reference genome sequence from long-read data have been done. We next aim to obtain genotype data for all TMM cohort participants (>150,000) using our custom SNP arrays. These data will help identify disease-associated genomic signatures in the Japanese population, while genomic data from TMM BirThree Cohort participants will be used to improve the reference genome panel. Follow-up of the cohort participants will allow us to test the genetic markers and, consequently, contribute to the realization of PHC.

Involvement of family members, especially grandparents, in genome epidemiological research is important to investigate both genetic and environmental factors of common diseases. The aim of the present study was to establish strategies to obtain enough number of family recruitment, especially focusing on grandparents, for the Tohoku Medical Megabank Birth and Three-Generation Cohort Study. Our main strategies are summarized below. 1) We standardized informed consent process with reference materials to help people understand the consent form, 2) we created an invitation letter to contact family members, and 3) we recruited family members in several settings. To obtain informed consent, we were careful of explaining clearly the complex reasons as well as drawing people's attention. By the end of March 2017, the number of invitation letters distributed to family members through the pregnant women was 23,806, including 18,702 grandparents. Among the grandparents who received invitation letters, 2,935 (15.7%) responded to us. Furthermore, some grandparents were asked to provide informed consent with other family members by staff at maternal clinics or Community Support Centers, and others directly booked Community Support Centers without responding to the invitation letter. Grandparents joined the study anytime during mother's maternal check-ups or delivery. Overall, 8,054 grandparents participated in our birth cohort study. The setting in which most grandparents were recruited was our own facilities. Importantly, both paternal and maternal grandparents more frequently participated in the study if the father also participated. In conclusion, we are able to recruit not only pregnant women but also fathers and grandparents.

Background: The association between eczema and mental health problems in schoolchildren has been underexplored. We aimed to investigate this association with the validated questionnaires., Methods: Of 46,648 invited children, we analyzed 9954 (21.3%) in the 2nd to the 8th grades from the ToMMo Child Health Study conducted in 2014 and 2015, a cross-sectional survey in Miyagi Prefecture, Japan. We defined eczema status as "normal," "mild/moderate," or "severe," based on the presence of persistent flexural eczema and sleep disturbance, according to the International Study of Asthma and Allergies in Childhood (ISAAC) Eczema Symptom Questionnaire. Clinical ranges of Strengths and Difficulties Questionnaire (SDQ) total difficulties scores and four SDQ subcategories of emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems were defined as scores ≥16, ≥5, ≥5, ≥7, and ≥5, respectively., Results: The mean SDQ total difficulties score significantly increased as eczema status worsened (all P ≤ 0.004 for trend). The OR of scores in the clinical range for SDQ total difficulties were 1.51 (95% CI, 1.31-1.74) for mild/moderate eczema and 2.63 (95% CI, 1.91-3.63) for severe eczema (P < 0.001 for trend), adjusted for sex, school grade, current wheeze, and disaster-related factors, using normal eczema as a reference. The association between severity of eczema and four SDQ subcategories showed a similar trend (all P ≤ 0.017 for trend)., Conclusions: We found a significant association between severity of eczema and mental health problems. The presence of eczema was associated with four SDQ subcategories., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Clarifying allele frequencies of disease-related genetic variants in a population is important in genomic medicine; however, such data is not yet available for the Japanese population. To estimate frequencies of actionable pathogenic variants in the Japanese population, we examined the reported pathological variants in genes recommended by the American College of Medical Genetics and Genomics (ACMG) in our reference panel of genomic variations, 2KJPN, which was created by whole-genome sequencing of 2049 individuals of the resident cohort of the Tohoku Medical Megabank Project. We searched for pathogenic variants in 2KJPN for 57 autosomal ACMG-recommended genes responsible for 26 diseases and then examined their frequencies. By referring to public databases of pathogenic variations, we identified 143 reported pathogenic variants in 2KJPN for the 57 ACMG recommended genes based on a classification system. At the individual level, 21% of the individuals were found to have at least one reported pathogenic allele. We then conducted a literature survey to review the variants and to check for evidence of pathogenicity. Our results suggest that a substantial number of people have reported pathogenic alleles for the ACMG genes, and reviewing variants is indispensable for constructing the information infrastructure of genomic medicine for the Japanese population.

Background: With the goal of realizing genome-based personalized healthcare, we have developed a biobank that integrates personal health, genome, and omics data along with biospecimens donated by volunteers of 150,000. Such a large-scale of data integration involves obvious risks of privacy violation. The research use of personal genome and health information is a topic of global discussion with regard to the protection of privacy while promoting scientific advancement. The present paper reports on our plans, current attempts, and accomplishments in addressing security problems involved in data sharing to ensure donor privacy while promoting scientific advancement., Methods: Biospecimens and data have been collected in prospective cohort studies with the comprehensive agreement. The sample size of 150,000 participants was required for multiple researches including genome-wide screening of gene by environment interactions, haplotype phasing, and parametric linkage analysis., Results: We established the T ohoku M edical M egabank (TMM) data sharing policy: a privacy protection rule that requires physical, personnel, and technological safeguards against privacy violation regarding the use and sharing of data. The proposed policy refers to that of NCBI and that of the Sanger Institute. The proposed policy classifies shared data according to the strength of re-identification risks. Local committees organized by TMM evaluate re-identification risk and assign a security category to a dataset. Every dataset is stored in an assigned segment of a supercomputer in accordance with its security category. A security manager should be designated to handle all security problems at individual data use locations. The proposed policy requires closed networks and IP-VPN remote connections., Conclusion: The mission of the biobank is to distribute biological resources most productively. This mission motivated us to collect biospecimens and health data and simultaneously analyze genome/omics data in-house. The biobank also has the mission of improving the quality and quantity of the contents of the biobank. This motivated us to request users to share the results of their research as feedback to the biobank. The TMM data sharing policy has tackled every security problem originating with the missions. We believe our current implementation to be the best way to protect privacy in data sharing.

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.

Unlabelled: Introduction The Great East Japan Earthquake of March 11, 2011 may have influenced the long-term health of those in the disaster area. It is important to collect current and future health information of the people living in the post-disaster area to provide appropriate health support and quality-oriented care. However, public perceptions of health and genomic studies in the Great East Japan Earthquake disaster area are still unknown., Methods: A questionnaire survey was conducted in one town affected by the Great East Japan Earthquake and subsequent tsunami. The results of the questionnaire were tailed and the differences in responses to each question were assessed by sex and age., Results: In 284 eligible people (137 men, 147 women), almost all participants agreed to join a health survey investigating the adverse effects of the disaster, and over 80% of the total participants agreed to genomic analysis. Over 70% of the participants wanted to receive pharmacogenetic testing and to receive feedback on which medications were suitable or unsuitable for them., Conclusions: Most people living in the disaster area are interested in health surveys. Most of the participants also showed interest in genomic analysis. Ishikuro M , Nakaya N , Obara T , Sato Y , Metoki H , Kikuya M , Tsuchiya N , Nakamura T , Nagami F , Kuriyama S , Hozawa A , the ToMMo Study Group. Public attitudes toward an epidemiological study with genomic analysis in the Great East Japan Earthquake disaster area. Prehosp Disaster Med. 2016;31(3):330-334.

After the Great East Japan Earthquake of 2011, there has been a concern about health problems among children. Therefore, we investigated the prevalence of wheeze and eczema symptoms and associated factors among children in areas primarily affected by the disaster. From 2012 to 2014, we distributed the parent-administered questionnaire to 25,198 children in all 233 public schools in the 13 municipalities of Miyagi Prefecture in northeast Japan. A total of 7,155 responses (mean age 10.5 ± 2.2 years) were received (response rate: 28.4%). The prevalence of allergic symptoms according to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in 2nd, 4th, 6th, and 8th graders was 12.4%, 9.9%, 9.3%, and 5.6% for wheeze, and 20.1%, 18.0%, 14.0%, and 12.4% for eczema. In multivariate logistic analysis, younger age, history of hospitalization, and difficulties in children's daily lives as assessed by the Strengths and Difficulties Questionnaire (SDQ), were significantly and consistently associated with both allergic symptoms (both P < 0.05). Living in a coastal municipality was also associated with eczema symptoms (P = 0.0278). The prevalence of eczema symptoms in the 2nd (20.1%) and 8th (12.4%) grades was significantly higher than previously reported in Japan. Living in a coastal municipality was independently associated with eczema symptoms, and psychometric properties were also closely linked to allergic symptoms. These findings are clinically important for understanding the risks of allergic disorders after natural disasters.

Residents of areas affected by the Great East Japan Earthquake may suffer from diseases or health problems. We are conducting a cross-sectional study from 2012 to 2015 to investigate and address the health needs of schoolchildren affected by this disaster. In this paper, we describe the protocol and research perspectives of our long-term child health study, and present the results obtained immediately after the disaster. The parent-administered questionnaire includes the International Study of Asthma and Allergies in Childhood questionnaire for asthma and eczema symptoms, the Strengths and Difficulties Questionnaire (SDQ), and a questionnaire on influenza infection and vaccination status. In 2012, we distributed the questionnaire to 3,505 (2nd, 4th, 6th, and 8th graders) in three municipalities located in southern coastal area among the 28 municipalities, and 1,277 (36.4%) returned the completed questionnaire. Mean age was 11.1 ± 2.2 years old. The number of children with symptoms of wheeze and eczema in the past 12 months was 146 (11.4%) and 199 (15.6%), respectively. The SDQ total difficulties score revealed 174 (13.6%) children with some form of difficulty in their daily lives. From May 2011 to April 2012, 195 (15.3%) and 649 (50.8%) children received the influenza vaccination once and twice, respectively, and 532 (41.7%) had suffered from influenza. The prevalence of eczema symptoms or some form of difficulty was higher than the Japanese average. However, careful interpretation was required because of potential self-selection bias from the low response rate. We will continue this study of schoolchildren to provide aggregate findings.

Most of the scanning force microscopy (SFM) images of supercoiled DNA on untreated mica thus far reported have not shown tight plectonemic structure seen by electron microscopy, but instead less coiled molecules and sometimes a partly "condensed" state with intimate chain-chain interactions. By observing time-lapse images of conformational changes of DNA induced by decreasing ionic strength of imaging buffer in solution SFM, we could show that the process of water rinsing, an indispensable step for preparation of dried samples, may be responsible for some of the conformational anomalies in the images previously reported. We have studied several protocols to observe supercoiled DNA molecules by SFM and discuss the merits and the demerits. Images obtained following uranyl acetate treatment may be ideal for the detection of DNA damage, as the supercoiled and nicked forms are easily distinguishable., ((c)2001 Elsevier Science.)