Koken Ozaki

The Tokyo Twin Cohort Project: Overview and initial findings

The Tokyo Twin Cohort Project (ToTCoP) is a large-scale longitudinal study of 5 years based on 1619 pairs of infant twins reared together. The purpose of the study is to construct a population-based twin registry in Japan and to investigate human growth and development and twin themselves. It covers behavioral, neurological, physical and environmental variables measured by questionnaire, home visiting and brain imaging technology. The full registry contains over 47,000 multiple births collected from the Basic Resident Register, and the targeted population is 3070 probable twins of 0 to 2 years old. Preliminary analysis of the entry questionnaire data showed no serious sampling biases. Descriptive statistics of parental characteristics (parental age, gestation age, parity and placentation, maternal weight, parenting stress) and childrens characteristics (body size at birth, 4 and 10 months of age, milk consumption, and sleeping and social behavior) and their correlations, genetic and environmental contributions and correlations are reported.

Using Non-Normal SEM to Resolve the ACDE Model in the Classical Twin Design

One of the biggest problems in classical twin studies is that it cannot estimate additive genetic (A), non-additive genetic (D), shared environmental (C), and non-shared environmental (E) effects, simultaneously, because the model, referred to as the ACDE model, has negative degrees of freedom when using Structural Equation Modeling (SEM). Therefore, instead of the ACDE model, the ACE model or the ADE model is actually used. However, using the ACE or ADE models almost always leads to biased estimates. In the present paper, the univariate ACDE model is developed using non-normal Structural Equation Modeling (nnSEM). In SEM, (1st- and) 2nd-order moments, namely, (means and) covariances are used as information. However, nnSEM uses higher-order moments as well as (1st- and) 2nd-order moments. nnSEM has a number of advantages over SEM. One of which is that nnSEM can specify models that cannot be specified using SEM because of the negative degrees of freedom. Simulation studies have shown that the proposed method can decrease the biases. There are other factors that have possible effects on phenotypes, such as higher-order epistasis. Since the proposed method cannot estimate these effects, further research on developing a more exhaustive model is needed.

Maternal and paternal indoor or outdoor smoking and the risk of asthma in their children: a nationwide prospective birth cohort study.

BACKGROUND Little is known about the differential impact of combinations of parental smoking behavior (indoor or outdoor smoking, or not smoking) on preventing childhood asthma. Our objective was to examine the association between parental smoking behavior and childrens asthma. METHODS A nationally representative population-based birth cohort of 40,580 babies, aged 0.5 years in 2001 (response rate, 87.8%), was studied to estimate adjusted odds ratios of combinations of maternal and paternal indoor or outdoor smoking at home for physician visits and hospitalization for childhood asthma up to 8-years-old, and population attributable fractions. RESULTS Odds of hospitalization for asthma among children whose father alone smokes indoors at home did not largely increase (up to 20%). However, if the mother also smokes indoors at home, the odds strongly increased. After adjusting for demographic, perinatal and socioeconomic factors, the increase in odds for children whose father and mother both smoke indoors compared to children with non-smoking parents was 54% (95% confidence interval: 21-96%), 43% (8-90%) and 72% (22-143%) for children aged 0.5<-2.5, 2.5<-4.5 and 4.5<-8 years-old, respectively. The odds ratios of smoking outdoors did not largely differ from those of smoking indoors. Our estimation of population attributable fractions revealed that if all parents in Japan quit smoking, hospitalization of children for asthma could be reduced by 8.3% (2.2-14.3%), 9.3% (0.9-17.6%) and 18.2% (7.7-28.8%), respectively. CONCLUSIONS Parental indoor smoking at home increased and exacerbated childrens asthma. Smoking at home, whether it is indoors or outdoors, may increase the risks for asthma attacks of their children.

Direction of causation between shared and non-shared environmental factors.

Determining the direction of causation between two related variables is an interesting and challenging problem. A simple regression model is a frequently used statistical tool to find out whether a dependent variable is significantly predicted by an independent variable; however using a simple regression model cannot determine the direction of causation, because the model fit takes no account of this direction. As an approach to this problem, non-normal structural equation modeling (nnSEM; Shimizu and Kano, J Stat Plan Inference 138:3483–3491, 2008) using higher order moments (third, fourth,…) as well as first and second order moments, can be useful. This method enables us to determine the direction of causation using goodness of fit, even for a simple regression model. In this paper, nnSEM is applied to behavior genetics, in particular, to the genetic simplex model. In this context, nnSEM enables us to determine the direction of causation between C (shared environment) factors and between E (non-shared environment) factors. The efficiency of this method is illustrated by simulation studies and the analysis of real longitudinal twin data.

Bidirectional influences between maternal parenting and children's peer problems: a longitudinal monozygotic twin difference study.

This twin study examined the bidirectional relationship between maternal parenting behaviors and childrens peer problems that were not confounded by genetic and family environmental factors. Mothers of 259 monozygotic twin pairs reported parenting behaviors and peer problems when twins were 42 and 48 months. Path analyses on monozygotic twin difference scores revealed that authoritative parenting (the presence of consistent discipline and lack of harsh parenting) and peer problems simultaneously influenced each other. Authoritative parenting reduced peer problems, and peer problems increased authoritative parenting. Neither consistent discipline nor harsh parenting alone was associated with peer problems. These results suggest that maternal authoritative parenting works protectively in regard to childrens peer problems, and peer problems can evoke such effective parenting.

Hyperactivity/inattention problems moderate environmental but not genetic mediation between negative parenting and conduct problems.

This study investigated the association between negative parenting (NP) and conduct problems (CP) in 6-year-old twins, taking into account the severity of hyperactivity/inattention problems (HIAP). Analyses of the data from 1,677 pairs of twins and their parents revealed that the shared environmental covariance between NP and CP was moderated by the level of HIAP but not by CP or NP, where the shared environmental covariance was larger in children with higher levels of HIAP than in children with lower levels of HIAP. The genetic covariance between NP and CP was not moderated by the level of HIAP, whereas it was larger in the group with lower levels of CP and NP than in the group with higher levels. These results suggest that severe HIAP strengthens shared environmental associations between NP and CP and that interventions focusing on the shared environmental component of NP would be effective for parents and children with severe HIAP.

Two cohort and three independent anonymous twin projects at the Keio Twin Research Center (KoTReC)

The Keio Twin Research Center has conducted two longitudinal twin cohort projects and has collected three independent and anonymous twin data sets for studies of phenotypes related to psychological, socio-economic, and mental health factors. The Keio Twin Study has examined adolescent and adult cohorts, with a total of over 2,400 pairs of twins and their parents. DNA samples are available for approximately 600 of these twin pairs. The Tokyo Twin Cohort Project has followed a total of 1,600 twin pairs from infancy to early childhood. The large-scale cross-sectional twin study (CROSS) has collected data from over 4,000 twin pairs, from 3 to 26 years of age, and from two high school twin cohorts containing a total of 1,000 pairs of twins. These data sets of anonymous twin studies have mainly targeted academic performance, attitude, and social environment. The present article introduces the research designs and major findings of our center, such as genetic structures of cognitive abilities, personality traits, and academic performances, developmental effects of genes and environment on attitude, socio-cognitive ability and parenting, genes x environment interaction on attitude and conduct problem, and statistical methodological challenges and so on. We discuss the challenges in conducting twin research in Japan.

DINA Models for Multiple-Choice Items With Few Parameters Considering Incorrect Answers

The deterministic-input, noisy “and” gate (DINA) model can judge whether an individual examinee has mastered each skill that is needed to answer an item correctly. This information is useful for students to know their deficits and for teachers to teach effectively. The DINA model is a statistical model for binary (correct or incorrect) data. However, recently a DINA model for multiple-choice items was developed by de la Torre. The model is aimed at obtaining information about students’ skills from incorrect answers. In the present study, new DINA models for multiple-choice items are developed that need many fewer parameters while still being able to express various answering probabilities without any restrictions on the form of the Q-matrix. Simulations using a Markov chain Monte Carlo method are performed to demonstrate the efficacies of the proposed models compared with the DINA model for binary data and the model of de la Torre for multiple-choice items, if appropriate starting values are set.

Joint and independent effect of alcohol and tobacco use on the risk of subsequent cancer incidence among cancer survivors: A cohort study using cancer registries

Drinking alcohol and smoking tobacco are major modifiable risk factors for cancer. However, little is known about whether these modifiable factors of cancer survivors are associated with subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. 27,762 eligible cancer survivors diagnosed between 1985 and 2007 were investigated for SPC until the end of 2008, using hospital‐based and population‐based cancer registries. The association between drinking, smoking and combined drinking and smoking (interaction) at the time of the first cancer diagnosis and incidence of SPCs (i.e., all SPCs, alcohol‐related, smoking‐related and specific SPCs) was estimated by Poisson regression. Compared with never‐drinker/never‐smoker, the categories ever‐drinker/ever‐smoker, current‐drinker/current‐smoker and heavy‐drinker/heavy‐smoker had 43–108%, 51–126% and 167–299% higher risk for all, alcohol‐related and tobacco‐related SPCs, respectively. The interaction of drinking and smoking had significantly high incidence rate ratios (IRRs) for SPCs among ever‐drinker/ever‐smoker and current‐drinker/current‐smoker, although ever drinking did not show a significant risk. Ever‐drinker/ever‐smoker had also significantly higher IRRs for esophageal and lung SPCs than never‐drinker/never‐smoker. Among comprehensive cancer survivors, ever and current drinkers only had a SPC risk when combined with smoking, while ever and current smokers had a SPC risk regardless of drinking status. Heavy drinking and heavy smoking were considered to be independent additive SPC risk factors. To reduce SPC incidence, it may be necessary (i) to reduce or stop alcohol use, (ii) to stop tobacco smoking and (iii) dual users, especially heavy users, should be treated as a high‐risk population for behavioral‐change intervention.

Genetic and environmental relationships between head circumference growth in the first year of life and sociocognitive development in the second year: a longitudinal twin study.

Although growth in head circumference (HC) during infancy is known to predict later childhood outcomes, the mechanisms underlying this association with later sociocognitive abilities remain undetermined. Thus, using a sample of 241 pairs of normally developing Japanese twins, this study investigated the underpinnings of the association between HC growth (difference between HC at birth and at 10 months) and sociocognitive abilities at 19 months as measured by 10 items from the M-CHAT. Phenotypic correlations between HC at birth and sociocognitive abilities and between HC growth and sociocognitive abilities were marginal and not significant. However, multivariate genetic analyses using Cholesky decomposition revealed that genetic influences on HC growth and those on sociocognitive abilities were negatively associated. On the other hand, shared and nonshared environmental influences on HC growth were positively associated with influences on sociocognitive abilities. Genetic and environmental influences on HC at birth were not significantly associated with influences on sociocognitive abilities. These results help to clarify the role of brain growth during infancy in the subsequent development of sociocognitive abilities and highlight the importance of examining the different roles of genetic and environmental influences in studies of these areas.