Are there causal relationships between attention-deficit/hyperactivity disorder and body mass index? Evidence from multiple genetically informed designs

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI) are associated. However, it remains unclear whether this association reflects causal relationships in either direction or confounding. Here, we implemented genetically informed methods to examine bidirectional causality and potential confounding. METHODS: Three genetically informed methods were employed: (i) cross-lagged twin-differences analyses to assess bidirectional effects of ADHD symptoms and BMI at ages 8, 12, 14 and 16 years in 2386 pairs of monozygotic twins from the Twins Early Development Study (TEDS); (ii) within- and between-family ADHD and BMI polygenic score (PS) analyses in 3320 pairs of dizygotic TEDS twins; and (iii) two-sample bidirectional Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) on ADHD (N = 55,374) and BMI (N = 806,834). RESULTS: Mixed results were obtained across the three methods. Twin-difference analyses provided little support for cross-lagged associations between ADHD symptoms and BMI over time. PS analyses were consistent with bidirectional relationships between ADHD and BMI, with plausible time-varying effects from childhood to adolescence. MR findings also suggested bidirectional causal effects between ADHD and BMI. Multivariable MR indicated the presence of substantial confounding in bidirectional relationships. CONCLUSIONS: The three methods converged to highlight multiple sources of confounding in the association between ADHD and BMI. PS and MR analyses suggested plausible causal relationships in both directions. Possible explanations for mixed causal findings across methods are discussed

The Associations between Callous-unemotional Traits and Symptoms of Conduct Problems, Hyperactivity and Emotional Problems: A Study of Adolescent Twins Screened for Neurodevelopmental Problems

Callous-unemotional (CU) traits (e.g., lack of empathy, lack of guilt, shallow affect) are associated with severe and persistent conduct problems in youth. There is evidence showing a substantial genetic correlation between CU traits and conduct problems. The etiological associations between CU traits and other psychopathological symptoms, including symptoms of hyperactivity and emotional problems (such as anxiety and depression symptoms), have been less explored. To examine the etiological associations between CU traits and symptoms of conduct problems, hyperactivity and emotional problems separately through the use of a twin design. Participants were same-sex twin pairs (n=426 twins; 42% female; 43% MZ; age=15) drawn from the Child and Adolescents Twin Study in Sweden, a longitudinal study of twins born in Sweden. The sample was mainly composed of children who screenpositive on neurodevelopmental problems/mental health problems or at-risk children (i.e., screen-negative children considered to be genetically at-risk siblings). We used self-report measures of CU traits, conduct problems, hyperactivity and emotional problems. Model-fitting analyses were conducted using structural equation modeling. We found a strong positive genetic correlation between CU traits and conduct problems and a moderate genetic correlation between CU traits and hyperactivity. We also found a relatively modest, but significant negative genetic correlation between CU traits and emotional problems. Using a sample of adolescent twins screened for neurodevelopmental problems, we replicated previous findings that showed a strong genetic correlation between CU traits and conduct problems and we extended research by examining further the etiological associations between CU traits and symptoms of hyperactivity and emotional problems

Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a "Question Mark Ear" (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations