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

Estimating disease prevalence using relatives of case and control probands.

We introduce a method of estimating disease prevalence from case-control family study data. Case-control family studies are performed to investigate the familial aggregation of disease; families are sampled via either a case or a control proband, and the resulting data contain information on disease status and covariates for the probands and their relatives. Here, we introduce estimators for overall prevalence and for covariate-stratum-specific (e.g., sex-specific) prevalence. These estimators combine the proportion of affected relatives of control probands with the proportion of affected relatives of case probands and are designed to yield approximately unbiased estimates of their population counterparts under certain commonly made assumptions. We also introduce corresponding confidence intervals designed to have good coverage properties even for small prevalences. Next, we describe simulation experiments where our estimators and intervals were applied to case-control family data sampled from fictional populations with various levels of familial aggregation. At all aggregation levels, the resulting estimates varied closely and symmetrically around their population counterparts, and the resulting intervals had good coverage properties, even for small sample sizes. Finally, we discuss the assumptions required for our estimators to be approximately unbiased, highlighting situations where an alternative estimator based only on relatives of control probands may perform better

Relative Influence of Genetics and Shared Environment on Child Mental Health Symptoms Depends on Comorbidity

<div><p>Background</p><p>Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes.</p><p>Methods</p><p>The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%).</p><p>Results</p><p>Latent class models delineated groups of children according to symptom profiles–not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a “Low Symptom” class to a “Moderately Internalizing & Severely Externalizing” class. In addition, a “Moderately Anxious” class was identified for girls but not boys, and a “Severely Impulsive & Inattentive” class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the “Low Symptom” and “Moderately Internalizing & Severely Externalizing” classes, and small to zero for other classes.</p><p>Conclusions</p><p>We conclude that symptom classes are largely similar across sexes in middle childhood. Heritability was moderate for all classes, but shared environment played a greater role for classes in which no one type of symptom predominated.</p></div

Proportion of variance accounted for (confidence intervals) and model fit of biometric twin models for girls and boys combined.

a<p>A, C, and E refer to proportion of variance accounted for by additive genetic, shared environment and unique environment, respectively.</p><p>Abbreviations: Sat = saturated model; ACE = twin model; LL = log-likelihood; Δχ<b><i>²</i></b> = delta chi square;</p><p>*p<.05,</p><p>**p<.01,</p><p>***p<.001.</p

Weighted^a averages of external covariates for girls, by latent class.

a<p>Weighted by class membership probabilities.</p>b<p>Income categories: 8 = $40,001 to$45,000; 9 = $45,001 to$50,000; 10 = $50,001 to$60,000; 11 = $60,001 to$70,000; 12 = $70,001 to$80,000.</p>c<p>Self Impairment Scale ranges from 0 (no impairment) to 1.9 (highest observed impairment) and Family Impairment Scale ranges from 0 (no impairment) to 2.8 (highest observed impairment).</p>d<p>Any diagnosis refers to a diagnosis of MDD, GAD, SAD, CD, ODD, or ADHD.</p><p>Abbreviations: MDD = Major Depressive Disorder; GAD = Generalized Anxiety Disorder; SAD = Separation Anxiety Disorder; CD = Conduct Disorder; ODD = Oppositional Defiant Disorder; ADHD = Attention-Deficit/Hyperactivity Disorder.</p

Item response plots for girls’ latent classes G5 and G1–G4 (upper panel) and girls’ latent classes G5 and G6–G9 (lower panel).

<p>Abbreviations: DE = Depression; OA = Overanxiousness; SA = Separation Anxiety; CN = Conduct Problems; OD = Oppositional Defiant Problems; IM = Impulsivity; AT = Inattention.</p

Weighted^a averages of external covariates for boys, by latent class.

a<p>Weighted by class membership probabilities.</p>b<p>Income categories: 8 = $40,001 to$45,000; 9 = $45,001 to$50,000; 10 = $50,001 to$60,000; 11 = $60,001 to$70,000; 12 = $70,001 to$80,000.</p>c<p>Self Impairment scale ranges from 0 (no impairment) to 1.9 (highest observed impairment) and Family Impairment Scale ranges from 0 (no impairment) to 3.0 (highest observed impairment).</p>d<p>Any diagnosis refers to a diagnosis of MDD, GAD, SAD, CD, ODD, or ADHD.</p><p>Abbreviations: MDD = Major Depressive Disorder; GAD = Generalized Anxiety Disorder; SAD = Separation Anxiety Disorder;</p><p>CD = Conduct Disorder; ODD = Oppositional Defiant Disorder; ADHD = Attention-Deficit/Hyperactivity Disorder.</p

Item response plots for boys’ latent classes B1 and B2–B5 (upper panel) and boys’ latent classes B1 and B6–B9 (lower panel).

<p>Abbreviations: DE = Depression; OA = Overanxiousness; SA = Separation Anxiety; CN = Conduct Problems; OD = Oppositional Defiant Problems; IM = Impulsivity; AT = Inattention.</p