Tohoku Medical Megabank Research Articles

Cumulative exposure to maternal psychological distress in the prenatal and postnatal periods and atopic dermatitis in children: findings from the TMM BirThree Cohort Study

BackgroundMaternal mental health problems in each of the prenatal period and postnatal period have been demonstrated as possible risk factors for atopic dermatitis (AD) in children. However, the cumulative impacts of maternal psychological distress in the prenatal and postnatal periods on AD in children remain unclear. This study examined the association between cumulative exposure to maternal psychological distress in the prenatal and postnatal periods and the development of AD in children.MethodsData were derived from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. In total, 8377 mother-child pairs in which the child had no AD at the age of 1 year were analyzed. Maternal psychological distress in early pregnancy and 1 year after delivery was defined as a K6 score ≥ 5, and the participants were categorized into four groups: no psychological distress in both the prenatal and postnatal periods; only the prenatal period; only the postnatal period; and both periods. The development of AD was defined as the presence of AD in a 2-year-old child without AD reported at the age of 1 year using the International Study of Asthma and Allergies in Childhood questionnaire. Generalized linear model analyses were conducted to examine the association between maternal psychological distress and the development of AD in children adjusted for age at delivery, educational attainment, smoking status in pregnancy, maternal history of AD, paternal history of AD, parity, maternal body mass index, and child sex.ResultsBetween the ages of 1 and 2 years, 14.0% of children developed AD. Maternal psychological distress in both prenatal and postnatal periods was associated with an increased risk of AD in children compared to no psychological distress in both periods (relative risk (RR), 95% confidence interval (CI): 1.34, 1.20–1.47). Maternal psychological distress in only the postnatal period was associated with an increased risk of AD in children (RR, 95% CI: 1.23, 1.07–1.39), but not in only the prenatal period (RR, 95% CI: 1.14, 0.98–1.30).ConclusionsCumulative exposure to maternal psychological distress in the prenatal and postnatal periods was associated with the development of AD in children.

Maternal Baseline Characteristics and Perinatal Outcomes: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

BackgroundThe Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study was launched in 2013 to evaluate the complex interactions of genetic and environmental factors in multifactorial diseases. The present study describes the maternal baseline profile and perinatal data of participating mothers and infants.MethodsExpectant mothers living in Miyagi Prefecture were recruited from obstetric facilities or affiliated centers between 2013 and 2017. Three sets of self-administered questionnaires were collected, and the medical records were reviewed to obtain precise information about each antenatal visit and each delivery. Biospecimens, including blood, urine, umbilical cord blood, and breast milk, were collected for the study biobank. The baseline maternal sociodemographic characteristics, results of screening tests, and obstetric outcomes were analyzed according to the maternal age group.ResultsA total of 23,406 pregnancies involving 23,730 fetuses resulted in 23,143 live births. Younger maternal participants had a tendency toward a higher incidence of threatened abortion and threatened premature labor, while older age groups exhibited a significantly higher rate of low lying placenta, placenta previa, gestational diabetes, and hypertensive disorders of pregnancy.ConclusionsThe present study clearly shows the distribution of maternal baseline characteristics and the range of perinatal outcomes according to maternal age group. This cohort study can provide strategic information for creating breakthroughs in the pathophysiology of perinatal, developmental, and noncommunicable diseases by collaborative data visiting or sharing.

Abstract TP199: Genome Wide Association Study Of Intracranial Artery Dissection Reveals Potential Novel Loci

Introduction: Cervico-cephalic dissections (extracranial artery dissection [EAD] and intracranial artery dissection [IAD]) are defined by a mural hematoma in the wall of a cervical or intracranial artery and represent an important cause of stroke in young adults. It is relatively uncommon in the general population and likely to represent the ethnic difference with higher frequency of IAD in Asian than European populations. A few studies examining the genetic contributions for these phenotypes were reported. In EAD, the PHACTR1 genes which had previously been identified as common genetic risk variants of hypertension and migraine was associated with EAD using genome-wide association study (GWAS) approaches. RNF213 , an important susceptibility gene for Moyamoya disease was associated with IAD in one small study (n=24) using a candidate-SNP analysis but no GWAS of IAD have been reported so far. We performed GWAS to identify common variants associated with IAD. Methods: A total of 100 Japanese patients with IAD based on imaging diagnostic criteria from multidisciplinary expert consensus were prospectively enrolled in National Cerebral and Cardiovascular Center from March 2011 to August 2018. Results: We performed GWAS in 100 IAD cases (61 men, 50 years of median age[IQR, 45-61]) and 8380 controls from the Tohoku Medical Megabank Project which is a publicly available healthy cohort. No variant reached to genome-wide significant but 14 variants (7 regions) showed nominal significant association with IAD (p < 10 -5 ). Among 14 variants, rs73828631 on RBMS3 gene showed highest association with IAD (odds ratio = 2.16, 95% confidence interval = 1.59-2.92; P = 3.08 х 10 -7 ). RBMS3 was previously identified as genetic loci associated with brain aneurysm. According to the Genotype-Tissue Expression (GTEx) project database, RBMS3 is highly expressed in artery. Conclusions: We identified potential 14 variants associated with IAD. We need to increase the number of IAD cases for further confirmation.

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

PurposeTo 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.DesignWe designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs).ParticipantsIn 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.MethodsEach 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 MeasuresWe identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages.ResultsIn 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.ConclusionsOur 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.

Relationship between the combination of polyunsaturated fatty acids intake and psychological distress during pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

No studies have examined the association of the combination of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs intake with psychological distress during pregnancy. To examine these associations, we divided Japanese pregnant women into 25 groups based on combining quintiles of n-3 PUFAs intake and quintiles of n-6 PUFAs intake. We conducted multivariable logistic regression analyses to assess the risk of psychological distress during pregnancy (Kessler Psychological Distress Scale ≥ 5 or 13). Compared to the third quintile of both n-3 PUFAs and n-6 PUFAs intake, the groups with unbalanced intake, high intake of both, and low intake of both were associated with a higher risk of both Kessler Psychological Distress Scale ≥ 5 and 13 in early and mid-pregnancy. Further research is needed to identify the precise combination of n-3 PUFAs and n-6 PUFAs intake associated with the lowest psychological distress during pregnancy

Consideration of the reference value and number of measurements of the urinary sodium-to-potassium ratio based on the prevalence of untreated home hypertension: TMM Cohort Study

The sodium-to-potassium (Na/K) ratio is known to be associated with blood pressure (BP). However, no reference value has been established since the urinary Na/K (uNa/K) ratio is known to have diurnal and day-to-day variations. Therefore, we investigated the number of days required to yield a better association between the morning uNa/K ratio and home BP (HBP) and determined a morning uNa/K ratio value that can be used as a reference value in participants who are not taking antihypertensive medication. This was a cross-sectional study using data from the Tohoku Medical Megabank Project Cohort Study. A total of 3122 participants borrowed HBP and uNa/K ratio monitors for 10 consecutive days. We assessed the relationship between the morning uNa/K ratio from 1 day to 10 days and home hypertension (HBP ≥ 135/85 mmHg) using multiple logistic regression models. Although a 1-day measurement of the morning uNa/K ratio was positively associated with home hypertension, multiple measurements of the morning uNa/K ratio were strongly related to home hypertension. The average morning uNa/K ratio was relatively stable after 3 days (adjusted odds ratio of home hypertension per unit increase in the uNa/K ratio for more than 3 days: 1.19–1.23). In conclusion, there was no threshold for the uNa/K ratio, and the morning uNa/K ratio was linearly associated with home hypertension. The Na/K ratio 2.0 calculated from the Dietary Reference Intakes for Japanese might be a good indication. Regarding the stability of the association between the morning uNa/K ratio and BP, more than 3 days of measurements is desirable.

A variant in orexin receptor-2 is associated with self-reported daytime sleepiness in the Japanese population.

Excessive daytime sleepiness is characterized by a persistent feeling of having trouble staying awake, typically with inappropriate sleep episodes. Orexin (hypocretin) is a neuropeptide that regulates sleep-wake cycles and rapid eye movement sleep. Several large-scale genome-wide association studies (GWASs) in European populations have found genetic variants in orexin receptor-1 (OX1R) and -2 (OX2R) that are associated with sleep traits including daytime sleepiness. To identify genetic variants associated with daytime sleepiness, we performed an association study of genetic variants in prepro-orexin, OX1R, and OX2R in 14,329 Japanese individuals from the Tohoku Medical Megabank Project cohort. A genetic variant in OX2R was significantly associated with self-reported daytime sleepiness after Bonferroni correction (rs188018846: P = 8.4E-05). In addition, a missense variant in OX2R identified by the European GWASs showed a nominally significant association with daytime sleepiness in a Japanese population (p.Ile308Val, rs2653349: P = 0.044). Multiple genetic variants in OX2R can affect daytime sleepiness in general populations.

The Contribution of Deleterious Rare Alleles in ENPP1 and Osteomalacia Causative Genes to Atypical Femoral Fracture.

Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10-5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10-5, OR 5.21, 95% CI 2.76-9.86). AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study

Introduction: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction, and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. Methods: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys <15 mL/min/1.73 m² or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. Results: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol, and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs. 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol/h/mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13–1.73) in G2 and 1.51 (1.30–1.84) in G3-G4. Conclusion: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction.

A Pilot Study for Return of Individual Pharmacogenomic Results to Population-Based Cohort Study Participants.

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.

Families' Health after the Great East Japan Earthquake: Findings from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Infectious diseases, chronic diseases, and mental disorders in both adults and children are reported after disasters occur. The correlation between chronic diseases and mental disorders has also been reported. Moreover, disasters may affect perinatal outcomes. Thus, both adult and child health should be carefully monitored in disaster aftermath. A prospective cohort study of pregnant women and their families, the Tohoku Medical Megabank Project (TMM) Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), has been conducted since 2013. A total of 73,529 family members participated in the TMM BirThree Cohort Study. Among siblings, the proportion of "small for gestational age" was the same in the pre- and post-disaster periods. Among parents and grandparents who answered the baseline questionnaire, 5.6% in the inland area and 19.8% in the coastal area had their houses totally/mostly destroyed by the Great East Japan Earthquake. Although a depression trend due to house damage was not observed in mothers, the proportion of psychological distress was high according to house damage (P for trend = 0.04). Among parents, there was an increase in overweight persons (P for trend = 0.004 in mothers and < 0.0001 in fathers) and in the number of smokers based on the severity of house damage (P for trend = 0.002 in mothers and < 0.0001 in fathers), whereas no such trend was observed in grandparents. Continuous monitoring and support for those who need are essential. Moreover, utilizing existing cohort studies to investigate health status when we face a new disaster is desirable.

Association between fat mass index, fat-free mass index and hemoglobin A1c in a Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

Aims/IntroductionFat mass and fat‐free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat‐free mass index with HbA1c.Materials and MethodsWe carried out a cross‐sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat‐free mass index were calculated as fat mass and fat‐free mass divided by the height squared, respectively. The indices were classified into sex‐specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat‐free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat‐free mass index, entering the number as a continuous term in the regression model.ResultsIn multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat‐free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat‐free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend).ConclusionsFat mass index was positively related to HbA1c levels. The fat‐free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes.

Social Predictors of Continued and Indoor Smoking Among Partners of Non-smoking Pregnant Women: The TMM BirThree Cohort Study.

BackgroundSecondhand smoke (SHS) from partners is a major source of exposure for non-smoking women. However, epidemiological studies have rarely examined social factors associated with continued and indoor smoking among pregnant women’s partners.MethodsWe analyzed data on 6,091 partners of non-smoking pregnant women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Partners’ age, education, income, workplace SHS exposure (almost never or sometimes, almost every day), and pregnant women’s smoking history (never, quit before pregnancy awareness, quit after pregnancy awareness) were used as social factors. Multiple logistic regression analyses were conducted to examine the associations of social factors with partners’ continued smoking and indoor smoking.ResultsAmong 2,432 smoking partners, 2,237 continued to smoke after pregnancy awareness. Workplace SHS exposure was associated with increased risk of partners’ continued smoking: the odds ratio of workplace SHS exposure almost every day compared with almost never or sometimes was 2.08 (95% confidence interval, 1.52–2.83). Women’s quitting smoking after—but not before—pregnancy awareness was associated with decreased risk of partners’ continued smoking: the odds ratio of women’s quitting after pregnancy awareness compared with never smoking was 0.57 (95% confidence interval, 0.40–0.80). About one-third of partners who continued to smoke did so indoors. Older age, lower education, workplace SHS exposure, and women’s quitting smoking after pregnancy awareness were associated with increased risk of partners’ indoor smoking.ConclusionsWorkplace SHS exposure and pregnant women’s smoking history were associated with continued smoking and indoor smoking among partners of non-smoking pregnant women.

DbTMM: an integrated database of large-scale cohort, genome and clinical data for the Tohoku Medical Megabank Project

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.

Living environments long-term after the Great East Japan Earthquake and nutritional intake among recent mothers.

Although large-scale natural disasters and the resultant changes in living environments worsen dietary habits among adults immediately after the disasters, whether this association remains for a long period is unclear. This is particularly important for recent mothers because lactating women require additional nutrition for milk production. Thus, we investigated the association of living environments with dietary habits and nutritional intake of recent mothers between four and seven years after the Great East Japan Earthquake (11th March, 2011). We analyzed 8,551 mothers who participated to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Living environments were characterized into four categories: "same home before the earthquake", "rental housing", "reconstructed home", and "acquaintance's home". Dietary habits and nutritional intake were evaluated using a food frequency questionnaire answered 12 months after their deliveries (the questionnaire was answered between March 2015 and July 2018). Multiple linear regression analyses demonstrated that mothers in 'rental housing' or 'reconstructed home' had a significantly lower intake of almost all nutrients or certain nutrients, respectively, compared with those residing in 'same home before the earthquake'. However, fewer significant differences were detected between the nutritional intake of the mothers lodging in an 'acquaintance's home' and that of those living in 'same home before the earthquake'. Our findings indicate that living environments long-term after largescale disasters are associated with dietary habits and nutritional intake among recent mothers.

One-year trajectories of postpartum depressive symptoms and associated psychosocial factors: findings from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

BackgroundTrajectories of postpartum depressive symptoms up to 1 year after childbirth and the related risk factors remain unclear. Accordingly, this study aimed to examine the 1-year trajectories of postpartum depressive symptoms and their associated risk factors. MethodsA total of 22,493 pregnant women were recruited between July 2013 and September 2016 in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. Among them, 11,668 women with no missing data were included in the analyses. Depressive symptoms were assessed at 1 month and 1 year postpartum using the Edinburgh Postnatal Depression Scale. Multinominal logistic regression analysis was conducted after adjusting for covariates. ResultsThe prevalence of depression was 13.9% at 1 month and 12.9% at 1 year postpartum. We identified four depression trajectories, i.e., “persistent (depressed throughout the 1 year postpartum)” (6.0%), “recovered (depressed at 1 month postpartum and recovered within a year)” (7.9%), “late-onset (became depressed after 1 month postpartum)” (6.8%), and “resilient (not depressed throughout 1 year postpartum)” (79.2%). Psychological distress during pregnancy was significantly associated with all trajectories (persistent: odds ratio [OR]=10.24, 95% confidence interval (CI)=8.40-12.48; recovered: OR=3.78, 95%CI=3.28-4.36; and late-onset: OR=3.96, 95%CI=3.40-4.62). LimitationsPostpartum depression was evaluated only by a self-administered questionnaire and the dropout rate was not neglectable. ConclusionsThis study highlighted the high prevalence of depressive symptoms at 1 year postpartum and found that half of the depressive symptoms at 1 year were late-onset. The findings suggest the necessity of long-term follow-up (up to 1 year) for perinatal mental health.

662Factors associated with smoking continuation and indoor smoking among pregnant women’s partners

Abstract Background Secondhand smoke by partners is a major source of exposure for non-smoking women. However, factors associated with smoking continuation and indoor smoking among pregnant women’s partners remain unknown. Methods We used data from 6348 partners of non-smoking pregnant women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from 2013 to 2017. Partners’ age, educational attainment, equivalent household income, and pregnant women’s smoking history (never, quitting before pregnancy awareness, quitting after pregnancy awareness) were used as explanatory variables. Multivariate logistic regression analyses were conducted to examine the associations between these variables and smoking continuation/indoor smoking of partners. Results Among 6348 partners, 2506 partners had been smokers at pregnancy awareness. Among them, the prevalence of smoking continuation after pregnancy awareness was 92.0%. Partners whose wives had quitted smoking after pregnancy awareness were less likely to continue smoking than partners whose wives had never smoked; the odds ratio was 0.57 (95% confidence interval, 0.41–0.80). Among partners who continued smoking, the prevalence of indoor smoking was 30.7%. Partners with ≤high school education were more likely to smoke indoors than partners with ≥university education; the odds ratio was 1.60 (95% confidence interval, 1.23–2.07). Conclusions Women’s smoking cessation after pregnancy awareness was associated with decreased risk of partners’ smoking continuation, and lower level of partners’ education was associated with increased risk of partners’ indoor smoking. Key messages Interventions for both women and their partners may be effective in reducing secondhand smoke exposure during pregnancy.

Spousal similarities in cardiometabolic risk factors: A cross-sectional comparison between Dutch and Japanese data from two large biobank studies

Background and aimsFew studies have examined and compared spousal concordance in different populations. This study aimed to quantify and compare spousal similarities in cardiometabolic risk factors and diseases between Dutch and Japanese populations. MethodsThis cross-sectional study included 28,265 Dutch Lifelines Cohort Study spouse pairs (2006–2013) and 5,391 Japanese Tohoku Medical Megabank Organization (ToMMo) Cohort Study pairs (2013–2016). Spousal similarities in cardiometabolic risk factors were evaluated using Pearson's correlation or logistic regression analyses adjusted for spousal age. ResultsThe husbands' and wives’ average ages in the Lifelines and ToMMo cohorts were 50.0 and 47.7 years and 63.2 and 60.4 years, respectively. Significant spousal similarities occurred with all cardiometabolic risk factors and diseases of interest in both cohorts. The age-adjusted correlation coefficients ranged from 0.032 to 0.263, with the strongest correlations observed in anthropometric traits. Spousal odds ratios [95% confidence interval] for the Lifelines vs. ToMMo cohort ranged from 1.45 (1.36–1.55) vs. 1.20 (1.05–1.38) for hypertension to 6.86 (6.30–7.48) vs. 4.60 (3.52–6.02) for current smoking. An increasing trend in spousal concordance with age was observed for sufficient physical activity in both cohorts. For current smoking, those aged 20–39 years showed the strongest concordance between pairs in both cohorts. The Dutch pairs showed stronger similarities in anthropometric traits and lifestyle habits (smoking and drinking) than their Japanese counterparts. ConclusionsSpouses showed similarities in several cardiometabolic risk factors among Dutch and Japanese populations, with regional and cultural influences on spousal similarities.

Associations of education and work status with alcohol use and cessation among pregnant women in Japan: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

BackgroundThere is inconsistent evidence on the associations of education and work status with alcohol use during pregnancy. Our aim was to examine the associations of education and work status with alcohol use and alcohol cessation during pregnancy in Japan.MethodsData were analyzed from 11,839 pregnant women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017 in Japan. Women were dichotomized as current drinkers or non-drinkers in both early and middle pregnancy. Alcohol cessation was defined as alcohol use in early pregnancy, but not in middle pregnancy. Multivariable log-binomial regression analyses were conducted to examine associations of education and work status with alcohol use in early and middle pregnancy and alcohol cessation, adjusted for age and income. The prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated by work status and education.ResultsThe prevalence of alcohol use in early and middle pregnancy was 20.9 and 6.4%, respectively. Higher education was associated with alcohol use in early pregnancy both among working and non-working women; the PRs of university education or higher compared with high school education or lower were 1.62 (95% CI, 1.34–1.96) and 1.29 (95% CI, 1.16–1.45), respectively. Higher education was associated with alcohol cessation during pregnancy among working women; the corresponding PR was 1.09 (95% CI, 1.01–1.17). Working was associated with alcohol use in early and middle pregnancy. Working was associated with a decreased probability of alcohol cessation among women with lower education but with an increased probability of alcohol cessation among women with higher education; the PRs of working compared with not working were 0.91 (95% CI, 0.82–1.00) and 1.10 (95% CI, 1.00–1.20), respectively.ConclusionsWomen with higher education were more likely to consume alcohol in early pregnancy and to cease alcohol use between early and middle pregnancy, especially working women. Working women were more likely to consume alcohol throughout pregnancy. Working women with lower education were less likely to cease alcohol use, whereas working women with higher education were more likely to cease alcohol use between early and middle pregnancy.

The return of individual genomic results to research participants: design and pilot study of Tohoku Medical Megabank Project.

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.