Fitting ACE Structural Equation Models to Case-Control Family Data

Investigators interested in whether a disease aggregates in families often collect case-control family data, which consist of disease status and covariate information for families selected via case or control probands. Here, we focus on the use of case-control family data to investigate the relative contributions to the disease of additive genetic effects (A), shared family environment (C), and unique environment (E). To this end, we describe a ACE model for binary family data and then introduce an approach to fitting the model to case-control family data. The structural equation model, which has been described previously, combines a general-family extension of the classic ACE twin model with a (possibly covariate-specific) liability-threshold model for binary outcomes. Our likelihood-based approach to fitting involves conditioning on the proband’s disease status, as well as setting prevalence equal to a pre-specified value that can be estimated from the data themselves if necessary. Simulation experiments suggest that our approach to fitting yields approximately unbiased estimates of the A, C, and E variance components, provided that certain commonly-made assumptions hold. These assumptions include: the usual assumptions for the classic ACE and liability-threshold models; assumptions about shared family environment for relative pairs; and assumptions about the case-control family sampling, including single ascertainment. When our approach is used to fit the ACE model to Austrian case-control family data on depression, the resulting estimate of heritability is very similar to those from previous analyses of twin data

Estimating the Prevalence of Disease Using Relatives of Case and Control Probands

We introduce a method for estimating the prevalence of disease using data from a case-control family study performed to investigate the aggregation of disease in families. The families are sampled via case and control probands, and the resulting data consist of information on disease status and covariates for the probands and their relatives. We introduce estimators for overall prevalence and for covariate stratum-specific prevalence (e.g., sex-specific prevalence) that yield approximately unbiased estimates of their population counterparts. We also introduce corresponding confidence intervals that have good coverage properties even for small prevalences. The estimators and intervals address the over-representation of diseased individuals in case-control family data by using only the relatives (of the probands) and by taking into account whether each relative was selected via a case or a control proband. Finally, we describe a simulation experiment in which the estimators and intervals were applied to case-control family datasets sampled from a fictional population that resembled the catchment area for an Austrian family study of major depressive disorder. The resulting estimates varied closely and symmetrically around their population counterparts, and the resulting intervals had good coverage properties

Conscientiousness predicts greater recovery from negative emotion

Greater levels of conscientiousness have been associated with lower levels of negative affect. We focus on one mechanism through which conscientiousness may decrease negative affect: effective emotion regulation, as reflected by greater recovery from negative stimuli. In 273 adults who were 35 - 85 years old, we collected self-report measures of personality including conscientiousness and its self-control facet, followed on average 2 years later by psychophysiological measures of emotional reactivity and recovery. Among middle-aged adults (35 - 65 years old), the measures of conscientiousness and self-control predicted greater recovery from, but not reactivity to, negative emotional stimuli. The effect of conscientiousness and self-control on recovery was not driven by other personality variables or by greater task adherence on the part of high conscientiousness individuals. In addition, the effect was specific to negative emotional stimuli and did not hold for neutral or positive emotional stimuli

Paternal age at childbirth and eating disorders in offspring

Background Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence. Method Data for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history. Results Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years ( v . the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED. Conclusions In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline

Gender specific early treatment for women with alcohol addiction (EWA): Impact on work related outcomes. A 25-year registry follow-up of a randomized controlled trial (RCT)

Background: Alcohol contributes to substantial economic burden, at both individual and community levels. We investigated the effect of the Early treatment for Women with Alcohol Addiction (EWA) treatment program on sickness leave, income, unemployment and early retirement pension up to 25 years following intake to treatment. Methods: The EWA RCT included 200 women with alcohol use disorder from 1983 to 1984 at the Karolinska University Hospital, Sweden. Participants were randomized to the EWA program, a two-year specialized woman only treatment including psychiatric, interpersonal and family concerns, or treatment as usual (TAU) in a mixed gender setting. We followed the participants in the RCT from 1985 to 2009 through linkage with a national labor market registry and applied latent growth curve modeling to estimate level and change in sickness leave, income, unemployment and early retirement pension. Findings: Relative to TAU, the EWA group had less increase in sickness leave up to 21 years after treatment. Overall, we found no differences in income between treatment groups, yet, a two-year interval analysis showed greater rise in income up to 8 years after treatment for the EWA group. Level and change in unemployment and early retirement pension did not differ between treatment groups. Conclusions: Gender specific treatment emphasizing psychiatric, interpersonal and family issues for women with alcohol addiction had long-term positive effects on sickness leave and income. These findings complement positive clinical outcomes of the EWA treatment program on drinking patterns, mental health and mortality.publishedVersio

Association Between Childhood to Adolescent Attention Deficit/Hyperactivity Disorder Symptom Trajectories and Late Adolescent Disordered Eating

Purpose Disordered eating is more prevalent among adolescents with attention deficit/hyperactivity disorder. Both inattention and hyperactivity/impulsivity symptoms show strong associations with disordered eating, but few investigations of these associations have been longitudinal. Thus, we examined the effect of childhood to adolescent inattention and hyperactivity/impulsivity symptom trajectories on late adolescent disordered eating. Methods We used growth mixture modeling to identify distinct inattention and hyperactivity/impulsivity symptom trajectories (called “classes”) across three time points (ages 8–9, 13–14, and 16–17 years) in the Swedish Twin study of CHild and Adolescent Development. The resulting classes were used to predict Eating Disorder Inventory-2 Bulimia, Drive for Thinness, and Body Dissatisfaction subscales at age 16–17 years, with adjustment for sex and body mass index at age 16–17 years. Results The combined inattention and hyperactivity/impulsivity symptom trajectory classes included: a “low symptom” class characterized by low inattention and hyperactivity/impulsivity throughout childhood/adolescence; a “predominantly inattention” class characterized by elevated inattention, but not hyperactivity/impulsivity, throughout childhood/adolescence; a “predominantly hyp/imp” class characterized by elevated hyperactivity/impulsivity, but not inattention, throughout childhood/adolescence; and a “both inattention and hyp/imp” class characterized by elevated inattention and hyperactivity/impulsivity throughout childhood/adolescence. After adjusting for sex and body mass index or sex and anxiety/depression symptoms, the “both inattention and hyp/imp” (vs. “low symptom”) class predicted significantly higher Eating Disorder Inventory-2 subscale scores during late adolescence. Conclusions Increased vigilance for disordered eating among children who have both inattention and hyperactivity/impulsivity symptoms throughout childhood and adolescence could aid in early identification of eating disorders

A Latent Variable Approach to Study Gene–Environment Interactions in the Presence of Multiple Correlated Exposures

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92103/1/j.1541-0420.2011.01677.x.pd

Latent variable models for gene–environment interactions in longitudinal studies with multiple correlated exposures

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110870/1/sim6401.pd

Paternal age at childbirth and eating disorders in offspring

Background. Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age’s relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence. Method. Data for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history. Results. Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED. Conclusions. In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.NonePublishe

Sex- and age-specific incidence of healthcare-register-recorded eating disorders in the complete swedish 1979-2001 birth cohort: INCIDENCE OF EATING DISORDERS

To investigate the sex- and age-specific incidence of healthcare-register-recorded anorexia nervosa (AN) and other eating disorders (OED) in a complete birth cohort, and assess whether incidence varies by diagnostic period and (sub-) birth cohort