Genetic Risk, Lifestyle Adherence, and Risk of Developing Hyperuricaemia in a Japanese Population.

OBJECTIVE: To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. METHODS: This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. RESULTS: Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61-12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736-0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751-0.819 for lifestyle and PRS; p = 0.07). CONCLUSION: : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.

A fine-scale genetic map of the Japanese population.

Genetic maps are fundamental resources for linkage and association studies. A fine-scale genetic map can be constructed by inferring historical recombination events from the genome-wide structure of linkage disequilibrium-a non-random association of alleles among loci-by using population-scale sequencing data. We constructed a fine-scale genetic map and identified recombination hotspots from 10 092 551 bi-allelic high-quality autosomal markers segregating among 150 unrelated Japanese individuals whose genotypes were determined by high-coverage (30×) whole-genome sequencing, and the genotype quality was carefully controlled by using their parents' and offspring's genotypes. The pedigree information was also utilized for haplotype phasing. The resulting genome-wide recombination rate profiles were concordant with those of the worldwide population on a broad scale, and the resolution was much improved. We identified 9487 recombination hotspots and confirmed the enrichment of previously known motifs in the hotspots. Moreover, we demonstrated that the Japanese genetic map improved the haplotype phasing and genotype imputation accuracy for the Japanese population. The construction of a population-specific genetic map will help make genetics research more accurate.

Dietary habits and plasma lipid concentrations in a general Japanese population.

INTRODUCTION: Accumulating data on the associations between food consumption and lipid composition in the body is essential for understanding the effects of dietary habits on health. OBJECTIVES: As part of omics research in the Tohoku Medical Megabank Community-Based Cohort Study, this study sought to reveal the dietary impact on plasma lipid concentration in a Japanese population. METHODS: We conducted a correlation analysis of food consumption and plasma lipid concentrations measured using mass spectrometry, for 4032 participants in Miyagi Prefecture, Japan. RESULTS: Our analysis revealed 83 marked correlations between six food categories and the concentrations of plasma lipids in nine subclasses. Previously reported associations, including those between seafood consumption and omega-3 fatty acids, were validated, while those between dairy product consumption and odd-carbon-number fatty acids (odd-FAs) were validated for the first time in an Asian population. Further analysis suggested that dairy product consumption is associated with odd-FAs via sphingomyelin (SM), which suggests that SM is a carrier of odd-FAs. These results are important for understanding odd-FA metabolism with regards to dairy product consumption. CONCLUSION: This study provides insight into the dietary impact on plasma lipid concentration in a Japanese population.

Deep exome sequencing identifies enrichment of deleterious mosaic variants in neurodevelopmental disorder genes and mitochondrial tRNA regions in bipolar disorder.

Bipolar disorder (BD) is a global medical issue, afflicting around 1% of the population with manic and depressive episodes. Despite various genetic studies, the genetic architecture and pathogenesis of BD have not been fully resolved. Besides germline variants, postzygotic mosaic variants are proposed as new candidate mechanisms contributing to BD. Here, we performed extensive deep exome sequencing (DES, ~300×) and validation experiments to investigate the roles of mosaic variants in BD with 235 BD cases (194 probands of trios and 41 single cases) and 39 controls. We found an enrichment of developmental disorder (DD) genes in the genes hit by deleterious mosaic variants in BD (P = 0.000552), including a ClinVar-registered pathogenic variant in ARID2. An enrichment of deleterious mosaic variants was also observed for autism spectrum disorder (ASD) genes (P = 0.000428). The proteins coded by the DD/ASD genes with non-synonymous mosaic variants in BD form more protein-protein interaction than expected, suggesting molecular mechanisms shared with DD/ASD but restricted to a subset of cells in BD. We also found significant enrichment of mitochondrial heteroplasmic variants, another class of mosaic variants, in mitochondrial tRNA genes in BD (P = 0.0102). Among them, recurrent m.3243 A > G variants known as causal for mitochondrial diseases were found in two unrelated BD probands with allele fractions of 5-12%, lower than in mitochondrial diseases. Despite the limitation of using peripheral tissues, our DES investigation supports the possible contribution of deleterious mosaic variants in the nuclear genome responsible for severer phenotypes, such as DD/ASD, to the risk of BD and further demonstrates that the same paradigm can be applied to the mitochondrial genome. These results, as well as the enrichment of heteroplasmic mitochondrial tRNA variants in BD, add a new piece to the understanding of the genetic architecture of BD and provide general insights into the pathological roles of mosaic variants in human diseases.

The effect of gestational diabetes mellitus on postnatal mother-infant bonding: Findings from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is associated with considerable psychological burden for women. In qualitative research, women with GDM describe increased awareness about their bonding with their infant, potentially resulting from the highly medicalised nature of the condition. The primary aim was to examine quantitatively whether GDM was associated with lower mother-infant bonding in the postnatal period. METHODS: Data were analysed from 10,419 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017 in Japan. GDM status was collected from hospital records and measured using the oral glucose tolerance test. Mother-infant bonding was assessed using the Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) at one-month postpartum, higher scores representing lower bonding. Data were analysed in SAS using multiple regression adjusting for relevant confounders. RESULTS: GDM did not appear to be associated with worse mother-infant bonding scores at one-month postpartum. There was a non-significant unadjusted trend in the mean mother-infant bonding scores (1.43(SD=1.11) versus (1.75(SD1.71)), and the proportion with bonding disorder (n = 4 (4.12%) versus n = 969 (9.39%)) in the GDM versus non GDM group respectively, indicating higher self-reported bonding in the GDM group. This remained not statistically significant in the adjusted analyses. CONCLUSIONS: We observed the reverse of our hypothesis, that there was a trend for women with GDM to self-report higher bonding compared to non-GDM women. There is need to replicate this finding in cohorts specifically designed to measure GDM-specific psychological distress.

Association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage.

OBJECTIVE: To evaluate the association between exposure to atypical antipsychotics during pregnancy and risk of miscarriage. MATERIAL AND METHODS: This nested case-control study used a large Japanese administrative database. Pregnancy onset and outcomes were estimated using previously reported algorithms, classifying cases as women becoming pregnant between 2013 and 2022 and ending in a miscarriage. Controls were randomly selected from the entire pregnancy cohort by risk-set sampling with replacement and were individually matched to the cases (3:1). The association between exposure to atypical antipsychotics and risk of miscarriage was assessed using conditional logistic regression adjusted for confounders. The association between benzodiazepine exposure and the risk of miscarriage was assessed as a positive control. RESULTS: In the cohort, 44,118 patients were matched with 132,317 controls. The mean ages (standard deviations) of the case and control groups were 33.3 (5.7) and 33.2 (5.5) years, respectively. The prevalence of atypical antipsychotics was 0.5% in both groups. Aripiprazole is an individual antipsychotic with the highest prescription prevalence. The adjusted odds ratios (aOR) for miscarriage were 0.966 (95% confidence interval [CI], 0.796-1.173) for atypical antipsychotics and 0.998 (0.784-1.269) for aripiprazole. A higher aOR (1.431, 95% CI 1.303-1.573) suggested an association with benzodiazepines. A sensitivity analysis that limited the population to women diagnosed with schizophrenia alone did not suggest an association between atypical antipsychotics and the risk of miscarriage. CONCLUSIONS: The results of this study do not suggest an association between exposure to atypical antipsychotics during pregnancy and the risk of miscarriage.

Medication use before and during pregnancy in Japan: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: To elucidate the status of medication use among pregnant women in Japan, by means of a multigenerational genome and birth cohort study: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). METHODS: Questionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (from July 2013 to March 2017) around 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed medication use over three periods: (1) 12 months prior to pregnancy diagnosis, (2) the period between pregnancy diagnosis and around week 12 of pregnancy, and (3) post around week 12 of pregnancy. RESULTS: In total, 19,297 women were included in the analysis. The proportion of pregnant women using medications was 49.0% prior to pregnancy diagnosis, 52.1% from diagnosis to week 12, and 58.4% post week 12 of pregnancy. The most frequently prescribed medications were loxoprofen sodium hydrate (5.5%) prior to pregnancy diagnosis, magnesium oxide (5.9%) from diagnosis to week 12, and ritodrine hydrochloride (10.5%) post week 12 of pregnancy. The number of women who used suspected teratogenic medications during early pregnancy was 96 prior to pregnancy diagnosis, 48 from diagnosis to week 12, and 54 post week 12 of pregnancy. CONCLUSION: We found that ~ 50% of the pregnant women used medications before and during pregnancy and some took potential teratogenic medications during pregnancy. In birth genomic cohort study, it is expected that investigations into the safety and effectiveness of medications used during pregnancy will advance.

Combined Fat Mass and Fat-free Mass Indices and Lung Function Among Japanese Population: The Tohoku Medical Megabank Community-based Cohort Study.

BACKGROUND: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other, since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. METHODS: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1-4 (lowest-highest), and entering the number as a continuous term in the regression model. RESULTS: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 was 3.0 (standard deviation [SD], 0.7) L for men and 2.3 (SD, 0.5) L for women. The mean FVC was 3.8 (SD, 0.7) L for men and 2.8 (SD, 0.5) L for women. FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. CONCLUSION: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.

Validity and reproducibility of food group intakes in a self-administered food frequency questionnaire for genomic and omics research: the Tohoku Medical Megabank Project.

BACKGROUND: The Tohoku Medical Megabank Project (TMM) was established to realize personalized healthcare and medicine using genomic and omics data. This study evaluated the validity and reproducibility of food group intakes derived from a self-administered food frequency questionnaire (TMM-FFQ) that included the response option "constitutionally unable to eat/drink it" among community-dwelling Japanese adults. METHODS: Participants comprised 89 men and 124 women aged ≥20 years from Miyagi Prefecture. Participants completed weighed food records (WFRs) for 3 consecutive days per season as reference intake and FFQs in 2019 (FFQ1) and 2021 (FFQ3). Spearman's rank correlation coefficients (CCs) were calculated for correlations between food group intakes estimated from the 12-day WFR and FFQ3 (validity), and for correlations between those estimated from the FFQ1 and FFQ3 (reproducibility). Cross-classification according to quintiles using FFQ and WFR data was also performed. RESULTS: The percentage of participants who chose the "constitutionally unable to eat/drink it" option was non-negligible for some food groups. In the validity analysis, CCs were >0.40 for many food groups; the median across 21 food groups was 0.49 in men and 0.45 in women. The median percentages of cross-classification into exact plus adjacent quintiles were 73.0% in men and 66.9% in women. In the reproducibility analysis, CCs were >0.50 for many food groups; the median across 21 food groups was 0.60 in men and 0.51 in women. CONCLUSIONS: The validity of the TMM-FFQ compared with 12-day WFR and the reproducibility of the TMM-FFQ were reasonable for food groups in the TMM cohort studies.

Progress Report of the Tohoku Medical Megabank Community-based Cohort Study: Study Profile of the Repeated Center-based Survey During Second Period in Miyagi Prefecture.

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.

Hypertensive disorders of pregnancy, neonatal outcomes and offspring developmental delay in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

INTRODUCTION: Developmental delay at an early age indicates the probability of continued problems after school age. Hypertensive disorders of pregnancy (HDP) are associated with developmental delays in offspring, with inconsistent outcomes. Neonatal outcomes vary according to HDP exposure and are relevant to development in later years. Here we aimed to clarify the relationship between HDP and developmental delay in offspring and whether neonatal outcomes mediate this association. MATERIAL AND METHODS: We used data from 5934 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study conducted in Japan between July 2013 and March 2017. The Ages and Stages Questionnaires, third edition, at 24 and 42 months of age, measured developmental delay in five areas. We performed multivariate quasi-Poisson regression and causal mediation analysis by neonatal outcomes. RESULTS: At 24 months of age, compared to offspring born from normotensive mothers, offspring born from HDP-affected mothers were more likely to experience developmental delay (risk ratio [RR] 1.29, 95% confidence interval [CI]: 1.09-1.52) in the areas of communication (RR 1.21, 95% CI: 1.00-1.45) and personal-social (RR 1.15, 95% CI: 1.03-1.28). This association was mediated by neonatal outcomes: preterm birth, neonatal asphyxia, NICU admission, and neonatal small head circumference. No association was observed between HDP and developmental delay at 42 months of age. CONCLUSIONS: Exposure to HDP during fetal life is associated with offspring developmental delay. This association is partly mediated by neonatal outcomes.

Genome-wide association study of nausea and vomiting during pregnancy in Japan: the TMM BirThree Cohort Study.

BACKGROUND: Nausea and vomiting during pregnancy (NVP) and hyperemesis gravidarum (HG), common conditions affecting most pregnant women, are highly heritable and associated with maternal and fetal morbidity. However, the pathologies underlying NVP and HG and their associated loci are scarce. METHODS: We performed genome-wide association studies (GWAS) of NVP in pregnant women (n = 23,040) who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from July 2013 to March 2017. Participants were divided into discovery (n = 9,464) and replication (n = 10,051) stages based on the platform used for their genotyping. Loci that achieved the genome-wide significance level (p < 5.0 × 10- 8) in the discovery stage were selected for genotyping in the replication stage. A meta-analysis integrating the discovery and replication stage results (n = 19,515) was conducted. NVP-related variables were identified as categorical or continuous. RESULTS: GWAS analysis in the discovery phase revealed loci linked to NVP in two gene regions, 11q22.1 (rs77775955) and 19p13.11 (rs749451 and rs28568614). Loci in these two gene regions have also been shown to be associated with HG in a White European population, indicating the generalizability of the GWAS analyses conducted in this study. Of these, only rs749451 and rs28568614 at 19p13.11 reached the genome-wide suggestive level (p < 1.0 × 10- 5) in the replication stage; however, both loci were significant in the meta-analysis. CONCLUSIONS: NVP-related loci were identified in the Japanese population at 11q22.1 and 19p13.11, as reported in previous GWAS. This study contributes new evidence on the generalizability of previous GWAS on the association between genetic background and NVP.

Associations of fasting plasma glucose and glycosylated hemoglobin levels at less than 24 weeks of gestation with hypertensive disorders of pregnancy: the BOSHI study.

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at <24 weeks of gestation with hypertensive disorders of pregnancy (HDP) and compare the strengths of the associations of HDP with FPG and HbA1c levels. Totally, 1,178 participants were included in this prospective cohort study. HDP, FPG, HbA1c, and potential confounding factors were included in multiple logistic regression models. The number of HDP cases was 136 (11.5%). When FPG and HbA1c were included in the model separately, quartile 4 (Q4) of FPG (87-125 mg/dL) and HbA1c (5.2-6.3% [33-45 mmol/mol]) levels had higher odds of HDP than quartile 1. The odds ratios (ORs) were 1.334 (95% confidence interval [CI]: 1.002-1.775) for Q4 of FPG and 1.405 (95% CI: 1.051-1.878) for Q4 of HbA1c. When the participants were divided into two categories based on the cut-off value with the maximum Youden Index of FPG or HbA1c, the ORs for high FPG (≥84 mg/dL) or high HbA1c (≥5.2% [33 mmol/mol]) were 1.223 (95% CI: 1.000-1.496) and 1.392 (95% CI: 1.122-1.728), respectively. When both FPG and HbA1c were included in the model simultaneously, the statistical significance of Q4 of FPG disappeared, whereas that of HbA1c remained. In two-category models, the same results were obtained. High FPG and HbA1c levels at <24 weeks of gestation were risk factors for HDP in pregnant Japanese women. In addition, high HbA1c levels were more strongly associated with HDP than high FPG levels.

Prospective associations of screen time at age 2 with specific behavioral subscales at age 3: a cohort study.

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.

Relationship between parity and the prevalence of chronic kidney disease in Japan considering hypertensive disorders of pregnancy and body mass index.

BACKGROUND: Global studies exploring the relationship between parity and chronic kidney disease (CKD) are scarce. Furthermore, no study has examined the relationship between parity and CKD in Japan. Therefore, this study aimed to examine the relationship between parity and the prevalence of CKD in a Japanese population, considering the clinical history of hypertensive disorders of pregnancy (HDP) and current body mass index (BMI) based on menopausal status. METHODS: This cross-sectional study included 26,945 Japanese multiparous women (5,006 premenopausal and 21,939 postmenopausal women) and 3,247 nulliparous women (1,599 premenopausal and 1,648 postmenopausal women). Participants were divided into two groups based on their menopausal status (premenopausal and postmenopausal women). The relationship between parity and the prevalence of CKD was evaluated using a multiple logistic regression model adjusted for several covariates, including a clinical history of HDP and current BMI. RESULTS: The relationship between parity and the prevalence of CKD was not statistically significant in either premenopausal or postmenopausal multiparous women. A clinical history of HDP was significantly associated with an increased risk of CKD in premenopausal and postmenopausal multiparous women. However, the relationship between a clinical history of HDP and CKD in premenopausal women was weakened after adjusting for current BMI. Furthermore, the current BMI was significantly associated with an increased risk of CKD in both premenopausal and postmenopausal women. CONCLUSIONS: Parity is not significantly associated with the prevalence of CKD in premenopausal and postmenopausal multiparous women. A clinical history of HDP is a risk factor for CKD in both premenopausal and postmenopausal women. Current BMI is also associated with an increased risk of CKD in premenopausal and postmenopausal women. Therefore, continuous surveillance and preventive measures against CKD should be provided to women with a clinical history of HDP. In addition, maintaining an appropriate body weight is beneficial in reducing the risk of CKD.

Association of physiological factors with grip and leg extension strength: tohoku medical megabank community-based cohort study.

BACKGROUND: Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. METHODS: We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. RESULTS: Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. CONCLUSIONS: Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.

The 2024 Noto Peninsula Earthquake and the Strategy of Medical Assistance from the Tohoku University Hospital.

A moment magnitude (Mw) 7.5 earthquake (the Global IDentifire (GLIDE) number: # Q-2024-000001-JPN) struck the Noto Peninsula of Ishikawa Prefecture on 1 January 2024 at 16:10 (Japan Standard Time). The reversed fault, 150 km in length and subducting beneath the peninsula, resulted in maximum seismic intensity 7 shaking, triggered the tsunami, destroyed over 43 thousand buildings, and disrupted roads and lifelines. The disaster claimed 236 deaths, including 15 indirect disaster deaths as of Jan. 28, 2024. There were Disaster Base Hospitals (DBHs) in the region, which survived structurally but suffered from impaired functions and the surge of medical needs of affected people. The disaster medical system of Japan immediately responded and coordinated the hundreds of emergency medical teams (EMTs), i.e., the Japan Disaster Medical Assistance Team (DMAT), from all over the country. Tohoku University Hospital, which had the experience of the 2011 Great East Japan Earthquake (GEJE), joined the coordinated response, dispatching a chain of DMATs, which helped the medical and public health coordination in Wajima City. The medical and public health needs included injuries, non-communicable diseases, infectious diseases, mental health issues, and maternal and child health issues, which were similar in the affected communities in GEJE. Although the actual damage far exceeded expectations, the structural retrofitting and business continuity plans of DBHs and the coordinated response of the national disaster medical system enhanced the effectiveness of medical and public health response.

Gap Volume Based on Computed Tomography Measurement Is a Strong Risk Factor for Delayed Gap Healing After Open-Wedge High Tibial Osteotomy.

PURPOSE: To identify factors that affect delayed gap healing after open-wedge high tibial osteotomy (OWHTO) and to determine whether large gap volume is a predictor of delayed gap healing. METHODS: This retrospective study analyzed biplane OWHTO performed between 2019 and 2023 for knee osteoarthritis or osteonecrosis. The minimum follow-up period was 1 year. Delayed gap healing was defined when the medial half of the osteotomy gap area had not reached the consolidation phase by 6 months after surgery based on anteroposterior knee radiographs. Gap volume was calculated from computed tomography images. Logistic regression was performed using body height, smoking, correction angle, hinge fracture, flange thickness, and gap volume. A gap volume cutoff value for delayed gap healing was determined with receiver operating characteristic curve analysis. Gap volume was predicted with multiple linear regression. RESULTS: There were 80 knees in 71 patients (36 men and 44 women). The mean gap volume was 7.6 cm3. Gap healing rates at 3, 6, 9, and 12 months after surgery were 26%, 65%, 89%, and 100%, respectively. There were 25 knees with delayed gap healing. Male sex was not a significant risk factor when adjusted for body height. Multivariate logistic regression revealed that only larger gap volume was a significant risk factor (odds ratio, 1.45; P = .006). The gap volume cutoff value was 7.6 cm3, with an area under the curve of 0.74. Tall body height and a large correction angle (both P < .001) were associated with a significantly larger gap volume (R2 = 0.73). CONCLUSIONS: Large gap volume is the most important risk factor for delayed gap healing after OWHTO. Gap volume can be predicted based on body height and correction angle. When OWHTO with substantial correction is planned for tall men, surgeons should be aware of possibly delayed gap healing. LEVEL OF EVIDENCE: Level IV, retrospective case-control study.

Identification of risk loci for postpartum depression in a genome-wide association study.

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.

Maternal social isolation and behavioral problems in preschool children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

It is essential to clarify factors associated with mental health and behavioral problems in early childhood, because children are critical stages of life for mental health. We aimed to prospectively examine the associations between maternal social isolation and behavioral problems in preschool children. We analyzed data from 5842 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores < 12) one year after delivery. The Child Behavior Checklist 1½-5 was used to assess behavioral problems, and its subscales were used to assess internalizing and externalizing problems in children at 4 years of age. Multiple logistic regression analyses were conducted to examine the associations between social isolation and behavioral problems, after adjustment for age, education, income, work status, marital status, extraversion, neuroticism, depressive symptoms, child sex, and number of siblings. Multiple logistic regression analyses were also conducted for internalizing problems and externalizing problems. The prevalence of maternal social isolation was 25.4%. Maternal social isolation was associated with an increased risk of behavioral problems in children: the odds ratio (OR) was 1.37 (95% confidence interval [CI] 1.14-1.64). Maternal social isolation was also associated with increased risks of internalizing problems and externalizing problems in children: the ORs were 1.33 (95% CI, 1.12-1.59) and 1.40 (95% CI, 1.18-1.66), respectively. In conclusion, maternal social isolation one year after delivery was associated with behavioral problems in children at 4 years of age.