Familial confounding or measurement error? How to interpret findings from sibling and co-twin control studies.

Epidemiological researchers often examine associations between risk factors and health outcomes in non-experimental designs. Observed associations may be causal or confounded by unmeasured factors. Sibling and co-twin control studies account for familial confounding by comparing exposure levels among siblings (or twins). If the exposure-outcome association is causal, the siblings should also differ regarding the outcome. However, such studies may sometimes introduce more bias than they alleviate. Measurement error in the exposure may bias results and lead to erroneous conclusions that truly causal exposure-outcome associations are confounded by familial factors. The current study used Monte Carlo simulations to examine bias due to measurement error in sibling control models when the observed exposure-outcome association is truly causal. The results showed that decreasing exposure reliability and increasing sibling-correlations in the exposure led to deflated exposure-outcome associations and inflated associations between the family mean of the exposure and the outcome. The risk of falsely concluding that causal associations were confounded was high in many situations. For example, when exposure reliability was 0.7 and the observed sibling-correlation was r = 0.4, about 30-90% of the samples (n = 2,000) provided results supporting a false conclusion of confounding, depending on how p-values were interpreted as evidence for a family effect on the outcome. The current results have practical importance for epidemiological researchers conducting or reviewing sibling and co-twin control studies and may improve our understanding of observed associations between risk factors and health outcomes. We have developed an app (SibSim) providing simulations of many situations not presented in this paper.

Genetic similarity between relatives provides evidence on the presence and history of assortative mating.

Assortative mating - the non-random mating of individuals with similar traits - is known to increase trait-specific genetic variance and genetic similarity between relatives. However, empirical evidence is limited for many traits, and the implications hinge on whether assortative mating has started recently or many generations ago. Here we show theoretically and empirically that genetic similarity between relatives can provide evidence on the presence and history of assortative mating. First, we employed path analysis to understand how assortative mating affects genetic similarity between family members across generations, finding that similarity between distant relatives is more affected than close relatives. Next, we correlated polygenic indices of 47,135 co-parents from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and found genetic evidence of assortative mating in nine out of sixteen examined traits. The same traits showed elevated similarity between relatives, especially distant relatives. Six of the nine traits, including educational attainment, showed greater genetic variance among offspring, which is inconsistent with stable assortative mating over many generations. These results suggest an ongoing increase in familial similarity for these traits. The implications of this research extend to genetic methodology and the understanding of social and economic disparities.

The structure of psychiatric comorbidity without selection and assortative mating.

The widespread comorbidity observed across psychiatric disorders may be the result of processes such as assortative mating, gene-environment correlation, or selection into population studies. Between-family analyses of comorbidity are subject to these sources of bias, whereas within-family analyses are not. Because of Mendelian inheritance, alleles are randomly assigned within families, conditional on parental alleles. We exploit this variation to compare the structure of comorbidity across broad psychiatric polygenic scores when calculated either between-family (child polygenic scores) or within-family (child polygenic scores regressed on parental polygenic scores) in over 25,000 genotyped parent-offspring trios from the Norwegian Mother Father and Child Cohort study (MoBa). We fitted a series of factor models to the between- and within-family data, which consisted of a single genetic p-factor and a varying number of uncorrelated subfactors. The best-fitting model was identical for between- and within-family analyses and included three subfactors capturing variants associated with neurodevelopment, psychosis, and constraint, in addition to the genetic p-factor. Partner genetic correlations, indicating assortative mating, were not present for the genetic p-factor, but were substantial for the psychosis (b = 0.081;95% CI [0.038,0.124]) and constraint (b = 0.257;95% CI [0.075,0.439]) subfactors. When average factor levels for MoBa mothers and fathers were compared to a population mean of zero we found evidence of sex-specific participation bias, which has implications for the generalizability of findings from cohort studies. Our results demonstrate the power of the within-family design for better understanding the mechanisms driving psychiatric comorbidity and their consequences on population health.

Intergenerational transmission of ADHD behaviors: genetic and environmental pathways.

BACKGROUND: We investigate if covariation between parental and child attention-deficit hyperactivity disorder (ADHD) behaviors can be explained by environmental and/or genetic transmission. METHODS: We employed a large children-of-twins-and-siblings sample (N = 22 276 parents and 11 566 8-year-old children) of the Norwegian Mother, Father and Child Cohort Study. This enabled us to disentangle intergenerational influences via parental genes and parental behaviors (i.e. genetic and environmental transmission, respectively). Fathers reported on their own symptoms and mothers on their own and their child's symptoms. RESULTS: Child ADHD behaviors correlated with their mother's (0.24) and father's (0.10) ADHD behaviors. These correlations were largely due to additive genetic transmission. Variation in children's ADHD behaviors was explained by genetic factors active in both generations (11%) and genetic factors specific to the children (46%), giving a total heritability of 57%. There were small effects of parental ADHD behaviors (2% environmental transmission) and gene-environment correlation (3%). The remaining variability in ADHD behaviors was due to individual-specific environmental factors. CONCLUSIONS: The intergenerational resemblance of ADHD behaviors is primarily due to genetic transmission, with little evidence for parental ADHD behaviors causing children's ADHD behaviors. This contradicts theories proposing environmental explanations of intergenerational transmission of ADHD, such as parenting theories or psychological life-history theory.

Non-random Mating Patterns in Education, Mental, and Somatic Health: A Population Study on Within- and Cross-Trait Associations.

Partners resemble each other on many traits, such as health and education. The traits are usually studied one by one in data from established couples and with potential participation bias. We studied all Norwegian parents who had their first child between 2016 and 2020 (N=187,926) and the siblings of these parents. We analysed grade point averages (GPA), educational attainment (EA), and medical records with prospective diagnostic data on 10 mental and 10 somatic health conditions measured 10 to 5 years before childbirth. We found stronger partner similarity in mental (median r=0.14) than in somatic health conditions (median r=0.04), with ubiquitous cross-trait correlations for mental health conditions (median r=0.13). GPA correlated 0.43 and EA 0.47 between partners. High GPA or EA was associated with better mental (median r=-0.16) and somatic (median r=-0.08) health in partners. Elevated correlations for mental health (median r=0.25) in established couples indicated convergence. Analyses of data on siblings and in-laws revealed deviations from direct assortment, suggesting instead indirect assortment based on related traits. GPA and EA accounted for 30-40% of the partner correlations in health. This has implications for the distribution of risk factors among children and for studies of intergenerational transmission.

Childhood personality and academic performance: A sibling fixed-effects study.

OBJECTIVE: This study investigated the associations between personality traits at age 8 and academic performance between ages 10 and 14, controlling for family confounds. BACKGROUND: Many studies have shown links between children's personality traits and their school performance. However, we lack evidence on whether these associations remain after genetic and environmental confounders are accounted for. METHOD: Sibling data from the Norwegian Mother and Child Cohort Study (MoBa) were used (n = 9701). First, we estimated the overall associations between Big Five personality traits and academic performance, including literacy, numeracy, and foreign language. Second, we added sibling fixed effects to remove unmeasured confounders shared by siblings as well as rating bias. RESULTS: Openness to Experience (between-person ß = 0.22 [95% CI: 0.21-0.24]) and Conscientiousness (between-person ß = 0.18 [95% CI 0.16-0.20]) were most strongly related to educational performance. Agreeableness (between-person ß = 0.06 [95% CI -0.08-0.04]) and Extraversion (between-person ß = 0.02 [95% CI 0.00-0.04]) showed small associations with educational performance. Neuroticism had a moderate negative association (between-person ß = -0.14 [95% CI -0.15-0.11]). All associations between personality and performance were robust to confounding: the within-family estimates from sibling fixed-effects models overlapped with the between-person effects. Finally, childhood personality was equally predictive of educational performance across ages and genders. CONCLUSIONS: Although family background is influential for academic achievement, it does not confound associations with personality. Childhood personality traits reflect unbiased and consistent individual differences in educational potential.

The association between parental internalizing disorders and child school performance.

Parents play a crucial role in children's lives. Despite high prevalences of anxiety and depression, we do not know how these disorders among parents associate with child school performance in Norway. We use regression models to estimate associations between parental mental disorders and child school performance, while adjusting for some social and genetic confounders. Parental anxiety and depression were assessed from administrative registers of government funded health service consultations for all individuals in Norway with children born between 1992 and 2002. School performance was assessed as standardized grade point average at the end of compulsory education when children are 16 years old. Associations were also considered in samples of adoptees and among differentially affected siblings. We find that 18.8% of children have a parent with an anxiety or depression diagnosis from primary care during the last three years of compulsory education (yearly prevalence: 11.5%). There is a negative association between these parental mental disorders and child school outcomes (z = 0.43). This association was weakened, but statistically significant among differentially exposed siblings (z = 0.04), while disappearing in adoptee children. Many children experience that their parents have anxiety or depression and receive a diagnosis from primary care. On average, these children have lower school performance. The association is attenuated when comparing differentially exposed siblings and disappears in adoptee children. These results have a poor fit with the hypothesis that parental internalizing is an influential causal factor in determining children's educational success.

Alcohol Intake and Academic Performance and Dropout in High School: A Prospective Cohort Study in 65,233 Adolescents.

PURPOSE: During the teenage years, many adolescents start drinking alcohol, and binge drinking is prevalent. We investigated the relationship between alcohol intake and academic performance. METHODS: We conducted a longitudinal cohort study by combining data from the Danish National Youth Study on 65,233 high school students aged 15-20 years, with information on dropout and grade point average. We assessed associations between alcohol intake and academic performance using multilevel Poisson regression and linear regression, accounting for dependency between students from the same school and class. RESULTS: The average alcohol intake was 10 drinks per week, and 43.6% engaged in binge drinking 3+ times per month. During follow-up, 9.8% of the boys and 6.7% of the girls dropped out. The incidence rate ratio was higher in never drinkers, frequent binge drinkers, and those with a high weekly alcohol intake as compared to those with a low intake. For example, the incidence rate ratio was 1.47 (95% confidence level: 1.24, 1.76) in girls who drank 21-27 drinks per week and 1.29 (95% confidence level: 1.13, 1.48) in girls who never drank as compared to those who drank <7 drinks per week. Alcohol associated with a lower grade point average over the entire span of intake in a dose-dependent manner, and similarly so in boys and girls. Findings were consistent in strata of socioeconomy and individual academic ambition. DISCUSSION: Alcohol intake has implications for academic performance and poses a threat for the prospects of the individual as well as society. Policies and interventions aimed at lowering the intake among high school students are warranted.

Prenatal maternal stress, child internalizing and externalizing symptoms, and the moderating role of parenting: findings from the Norwegian mother, father, and child cohort study.

BACKGROUND: Few studies have examined how parenting influences the associations between prenatal maternal stress and children's mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations. METHODS: This study is based on 15 963 mother-child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques. RESULTS: Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased. CONCLUSIONS: This study confirms associations between prenatal maternal stress and children's mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

Social anxiety disorder is a risk factor for alcohol use problems in the National Comorbidity Surveys.

BACKGROUND: According to the self-medication and biopsychosocial models, individuals with social anxiety disorder (SAD) are at increased risk of developing an alcohol use disorder (AUD) as alcohol represents a maladaptive coping mechanism for some sufferers of SAD. The SAD-to-AUD causation was earlier supported in Norwegian longitudinal twin data and later questioned using longitudinal data from the USA. METHODS: We re-analyzed partly the same USA-based data (National Comorbidity Surveys, n = 5001), conducting theoretical and simulation analyses on different formulations of temporality and using real-data Logistic regression analysis to investigate whether baseline SAD was associated with AUD at the follow-up. RESULTS: Upon proper analysis of temporality, SAD preceded AUD. Specifically, SAD was the only one of the seven anxiety disorders that predicted 10-year later AUD after adjusting for all other anxiety disorders and AUD at the baseline (odds ratio was 1.70% and 95% confidence interval 1.12-2.57). SAD was also associated with incident AUD (OR = 1.64, 95% CI = 1.14-2.37). We provide formal, simulation-based, and data-based arguments on how certain flawed models of incidence attenuate the temporal association. CONCLUSIONS: We demonstrated temporality and specificity in SAD-to-AUD association, which are considered signs of causation. We further identified and discussed problems in previous statistical analyses with different conclusions. Our findings add support for models positing causal effects of SAD on AUD, such as the self-medication and biopsychosocial models. The available evidence suggests that treating SAD should incur better chances of preventing AUD compared to treating other anxiety disorders, which lack comparable evidence on causation.

Intergenerational effects of parental educational attainment on parenting and childhood educational outcomes: Evidence from MoBa using within-family Mendelian randomization.

The intergenerational transmission of educational attainment from parents to their children is one of the most important and studied relationships in social science. Longitudinal studies have found strong associations between parents' and their children's educational outcomes, which could be due to the effects of parents. Here we provide new evidence about whether parents' educational attainment affects their parenting behaviours and children's early educational outcomes using within-family Mendelian randomization and data from 40,879 genotyped parent-child trios from the Norwegian Mother, Father and Child Cohort (MoBa) study. We found evidence suggesting that parents' educational attainment affects their children's educational outcomes from age 5 to 14. More studies are needed to provide more samples of parent-child trios and assess the potential consequences of selection bias and grandparental effects.

Positive maternal mental health attenuates the associations between prenatal stress and children's internalizing and externalizing symptoms.

Positive maternal mental health can improve perceptions of stressful situations and promote the use of adaptive coping strategies. However, few studies have examined how positive maternal mental health affects children's development. The aims of this study were to examine the associations between positive maternal mental health and children's internalizing and externalizing symptoms, and to ascertain whether positive maternal mental health moderated the associations between prenatal stress and children's internalizing and externalizing symptoms. This study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa), and comprised 36,584 mother-child dyads. Prenatal stress was assessed using 41 self-reported items measured during pregnancy. Positive maternal mental health (self-efficacy, self-esteem, and enjoyment) was assessed by maternal report during pregnancy and postpartum. Child internalizing and externalizing symptoms were assessed by maternal report at age 5. Structural equation modeling was used for analysis. Maternal self-efficacy, self-esteem, and enjoyment were negatively associated with internalizing and externalizing symptoms in males and females. The association between prenatal stress and internalizing symptoms in males was stronger at low than at high levels of maternal self-esteem and enjoyment, whereas for females, the association was stronger at low than at high levels of maternal self-esteem and self-efficacy. This study provides evidence of associations between positive maternal mental health and children's mental health, and suggests that higher positive maternal mental health may buffer against the impacts of prenatal stress. Positive maternal mental health may represent an important intervention target to improve maternal-child well-being and foster intergenerational resilience.

The educational burden of disease: a cohort study.

BACKGROUND: Students with health disorders might be at risk of disengaging from education, which can reinforce socioeconomic inequalities in health. We aimed to evaluate the associations between 176 diseases and injuries and later school performance in Norwegian adolescents and to estimate the importance of each disorder using a novel measure for the educational burden of disease (EBoD). METHODS: We used diagnostic information from government-funded health services for all Norwegian inhabitants who were born between Jan 1, 1995, and Dec 31, 2002, were registered as living in Norway at age 11-16 years, and were participating in compulsory education. School performance was assessed as grade point average at the end of compulsory education at age 16 years. We used a linear regression of school performance on disease in a fixed-effects sibling comparison model (113 411 families). The association (regression coefficients) between disease and school performance was multiplied by disease prevalence to estimate the proportional EBoD among 467 412 individuals participating in compulsory education. FINDINGS: Overall, although most diseases were not meaningfully associated with grade point average (regression coefficients close to 0), some were strongly associated (eg, intellectual disability regression coefficients -1·2 for boys and -1·3 for girls). The total educational disease burden was slightly higher for girls (53·5%) than for boys (46·5%). Mental health disorders were associated with the largest educational burden among adolescents in Norway (total burden 44·6%; boys 24·6% vs girls 20·0%), of which hyperkinetic disorder contributed to 22·1% of the total burden (boys 14·6% vs girls 7·5%). Among somatic diseases, those with unknown causes and possibly mental causes were associated with the largest educational burden. INTERPRETATION: The EBoD concept could provide a simple metric to guide researchers and policy makers. Because mental health disorders form a large component of the educational burden, investment in mental health might be particularly important for improving educational outcomes in adolescents. FUNDING: The Research Council of Norway.

Modeling assortative mating and genetic similarities between partners, siblings, and in-laws.

Assortative mating on heritable traits can have implications for the genetic resemblance between siblings and in-laws in succeeding generations. We studied polygenic scores and phenotypic data from pairs of partners (n = 26,681), siblings (n = 2,170), siblings-in-law (n = 3,905), and co-siblings-in-law (n = 1,763) in the Norwegian Mother, Father and Child Cohort Study. Using structural equation models, we estimated associations between measurement error-free latent genetic and phenotypic variables. We found evidence of genetic similarity between partners for educational attainment (rg = 0.37), height (rg = 0.13), and depression (rg = 0.08). Common genetic variants associated with educational attainment correlated between siblings above 0.50 (rg = 0.68) and between siblings-in-law (rg = 0.25) and co-siblings-in-law (rg = 0.09). Indirect assortment on secondary traits accounted for partner similarity in education and depression, but not in height. Comparisons between the genetic similarities of partners and siblings indicated that genetic variances were in intergenerational equilibrium. This study shows genetic similarities between extended family members and that assortative mating has taken place for several generations.

Educational attainment and mortality in schizophrenia.

BACKGROUND: Individuals suffering from schizophrenia have a reduced life expectancy with cardiovascular disease (CVD) as a major contributor. Low educational attainment is associated with schizophrenia, as well as with all-cause and CVD mortality. However, it is unknown to what extent low educational attainment can explain the increased mortality in individuals with schizophrenia. AIM: Here, we quantify associations between educational attainment and all-cause and CVD mortality in individuals with schizophrenia, and compare them with the corresponding associations in the general population. METHOD: All Norwegian citizens born between January 1, 1925, and December 31, 1959, were followed up from January 1, 1990, to December 31, 2014. The total sample included 1,852,113 individuals, of which 6548 were registered with schizophrenia. We estimated hazard ratios (HR) for all-cause and CVD mortality with Cox models, in addition to life years lost. Educational attainment for index persons and their parents were included in the models. RESULTS: In the general population individuals with low educational attainment had higher risk of all-cause (HR: 1.48 [95% CI: 1.47-1.49]) and CVD (HR: 1.59 [95% CI: 1.57-1.61]) mortality. In individuals with schizophrenia these estimates were substantially lower (all-cause: HR: 1.13 [95% CI: 1.05-1.21] and CVD: HR: 1.12 [95% CI: 0.98-1.27]). Low educational attainment accounted for 3.28 (3.21-3.35) life years lost in males and 2.48 (2.42-2.55) years in females in the general population, but was not significantly associated with life years lost in individuals with schizophrenia. Results were similar for parental educational attainment. CONCLUSIONS: Our results indicate that while individuals with schizophrenia in general have lower educational attainment and higher mortality rates compared with the general population, the association between educational attainment and mortality is smaller in schizophrenia subjects than in the general population.

The ADHD deficit in school performance across sex and parental education: A prospective sibling-comparison register study of 344,152 Norwegian adolescents.

Background: Attention-Deficit Hyperactivity Disorder (ADHD) is associated with impaired school performance, but the impact of ADHD may vary across sex, family background, and school subjects. By using prospective population-wide register data, we describe impairment in academic performance related to ADHD across different school subjects and investigate how this impairment differ across sex and parental education. Methods: We examined grades and Grade Point Averages (GPA) at age ∼16 among 344,152 Norwegian children born between 1997 and 2002. We linked grades with diagnoses from publicly funded general practitioners and with demographic information. Associations between ADHD diagnosed between age 10 and 16 and school performance were estimated with linear models, including sibling-models which control for unobserved variables shared within families. Results: Children with ADHD (4.0%) had -1.11 standard deviations lower GPAs compared to children without ADHD. This difference remained substantial after adjusting for demographic factors (-0.87), comorbid mental disorders (-0.82), early school performance (-0.54), and when comparing full siblings (-0.60). The relative ADHD deficit was 22% larger for girls than for boys and 39% larger for children with highly educated parents than for children of parents without completed high school, but the absolute deficit was smaller. Conclusion: The ADHD deficit in school performance was large and not easily attributable to other factors. Because the ADHD deficit was large in all school subjects, interventions should ideally address factors that affect school performance broadly, although targeting theoretical subjects specifically may be most effective given limited resources.

Prenatal work stress is associated with prenatal and postnatal depression and anxiety: Findings from the Norwegian Mother, Father and Child Cohort Study (MoBa).

BACKGROUND: An emerging body of research suggests that stress experienced in the workplace can have detrimental impacts on maternal mental health, including greater risk of postnatal depression. However, few longitudinal studies have examined these associations during the perinatal period. The objective of this study was to examine the associations between prenatal work stress and subsequent depression and anxiety. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa), and included 77,999 employed women recruited between 1999 and 2008. The exposure variable was prenatal work stress measured at 17 weeks' gestation, using an 8-item scale examining factors including autonomy, working relationships, and work enjoyment. Outcomes included depression and anxiety at 30 weeks' gestation and 6 months postpartum, measured using the Symptom Checklist-8. Analyses comprised of unadjusted and adjusted logistic regressions. RESULTS: After covariate adjustment, prenatal work stress was associated with depression and anxiety at 30 weeks' gestation (OR = 1.33, 95% CI: 1.19-1.49), and 6 months postpartum (OR = 1.44, 95% CI: 1.28-1.61). Most associations remained after adjustment for additional work-related variables and maternity leave. LIMITATIONS: Work stress was measured once during pregnancy, thus variation of associations by trimester could not be investigated. Findings are reported for a sample with high socioeconomic status, and may not generalize to other populations. CONCLUSIONS: Women dealing with work stress during pregnancy are more likely to experience subsequent depression and anxiety. Findings can inform the development of workplace strategies to support the mental health of expecting and new mothers.

Parental binge drinking and offspring's high school non-completion: A prospective HUNT survey and educational registry study.

BACKGROUND: Alcohol-use disorders (AUD) in parents are associated with adverse outcomes in offspring. It is less known whether other forms of parental drinking such as binge drinking may also be a risk factor for offspring's outcomes -- specifically, high school non-completion. METHODS: These questions were examined in a sample of 3101 offspring (Mage = 16.1 , SD = 1.68; 49.5% girls) from 2510 2-parent families who participated in the Nord-Trøndelag Health Study in Norway (HUNT3; Young-HUNT3) in 2006-08 and were followed-up through the National Education Database (NUDB) until 2014. Associations between maternal and paternal binge drinking patterns as reported in HUNT during offspring's adolescence and offspring's subsequent high school completion were examined using logistic regression models while accounting for a comprehensive set of socio-demographic, parental, and offspring characteristics as assessed at HUNT baseline. Effect modifications of these putative associations by offspring characteristics were also explored. FINDINGS: Approximately 1 in 6 offspring (13.6% girls, 21.1% boys) failed to graduate high school within the officially designated time period, while roughly 1 in 5 mothers (20.4%) and 1 in 2 fathers (51.2%) reported any binge drinking. Weekly or more frequent binge drinking in fathers was prospectively associated with more than doubled odds of high school non-completion in offspring; OR = 2.23, 95% CI = 1.50-3.31. This effect remained substantively identical after adjustment for all covariates (aOR = 2.20, 95% CI = 1.38-3.50) and uniform across offspring characteristics such as gender, academic orientation and performance, anxiety and depression, typical alcohol consumption, and witnessing parental intoxication as assessed at HUNT baseline. CONCLUSIONS: Weekly or more frequent binge drinking in fathers negatively affected high school graduation prospects in their offspring.

Parental income and mental disorders in children and adolescents: prospective register-based study.

BACKGROUND: Children with low-income parents have a higher risk of mental disorders, although it is unclear whether other parental characteristics or genetic confounding explain these associations and whether it is true for all mental disorders. METHODS: In this registry-based study of all children in Norway (n = 1 354 393) aged 5-17 years from 2008 to 2016, we examined whether parental income was associated with childhood diagnoses of mental disorders identified through national registries from primary healthcare, hospitalizations and specialist outpatient services. RESULTS: There were substantial differences in mental disorders by parental income, except for eating disorders in girls. In the bottom 1% of parental income, 16.9% [95% confidence interval (CI): 15.6, 18.3] of boys had a mental disorder compared with 4.1% (95% CI: 3.3, 4.8) in the top 1%. Among girls, there were 14.2% (95% CI: 12.9, 15.5) in the lowest, compared with 3.2% (95% CI: 2.5, 3.9) in the highest parental-income percentile. Differences were mainly attributable to attention-deficit hyperactivity disorder in boys and anxiety and depression in girls. There were more mental disorders in children whose parents had mental disorders or low education, or lived in separate households. Still, parental income remained associated with children's mental disorders after accounting for parents' mental disorders and other factors, and associations were also present among adopted children. CONCLUSIONS: Mental disorders were 3- to 4-fold more prevalent in children with parents in the lowest compared with the highest income percentiles. Parents' own mental disorders, other socio-demographic factors and genetic confounding did not fully explain these associations.