Research Review: The strength of the genetic overlap between ADHD and other psychiatric symptoms – a systematic review and meta‐analysis

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with other psychiatric disorders. Twin studies have established that these co-occurrences are in part due to shared genetic risks. However, the strength of these genetic overlaps and the potential heterogeneity accounted for by type of psychiatric symptoms, age, and methods of assessment remain unclear. We conducted a systematic review to fill this gap. Methods: We searched PubMed, PsycINFO, Embase, and Web of Science until March 07, 2019. Genetic correlations (r g) were used as effect size measures. Results: A total of 31 independent studies fulfilled the inclusion criteria. The pooled estimates showed that the associations between ADHD and other psychiatric symptoms were partly explained by shared genetic factors, with a pooled genetic correlation of 0.50, 95% confidence interval: 0.46-0.60. The genetic correlations (r g) between ADHD and externalizing (r g = .49 [0.37-0.61]), internalizing (r g = .50 [0.39-0.69]), and neurodevelopmental (r g = .56 [0.47-0.66]) symptoms were similar in magnitude. The genetic correlations in childhood and adulthood were r g = .53 (0.43-0.63) and r g = .51 (0.44-0.56), respectively. For methods of assessment, the genetic correlations were also similar in strength, self-reports r g = .52 (0.47-0.58), other informants r g = .55 (0.41-0.69), and combined raters r g = .50 (0.33-0.65). Conclusions: These findings indicate that the cooccurrence of externalizing, internalizing, and neurodevelopmental disorder symptoms in individuals with ADHD symptoms in part is due to a shared genetic risk.

ADHD is more closely linked to neurodevelopmental than externalizing and internalizing disorders: A genetically informed multivariate Swedish population study

“…The phenotypic correlations between ADHD and the neurodevelopmental, externalizing and internalizing subfactors were all strong, and were moderately-tostrongly influenced by genetic variation, in line with previous research (21,30,49,50).…”

“…The correlated factors model (RMSEA=0.006, CFI=0.974) revealed that the three neurodevelopmental, externalizing and internalizing subfactors were moderately-tostrongly intercorrelated (r=0.46-0.77), and were all significantly and strongly correlated with ADHD (r=0.67-0.75). The magnitude of correlations, along with the heritabilities and co-heritabilities of the subfactors and ADHD, were overall in line with previous research ( Figure S1) (11,21,24,27,35,49,50). The bifactor model (RMSEA=0.004, CFI=0.982) revealed very similar within-individual and betweensibling correlations of ADHD with the general and specific factors compared to the higher-order model ( Figure S2 & Table S13).…”

Overlap between attention-deficit hyperactivity disorder and neurodevelopmental, externalising and internalising disorders: separating unique from general psychopathology effects

“…The phenotypic correlations between ADHD and the neurodevelopmental, externalising and internalising subfactors were all strong, and were moderately to strongly influenced by genetic variation, in line with previous research. 8,16,32,33 After accounting for the general psychopathology factor, the correlation between ADHD and the neurodevelopmental-specific factor remained moderately strong, and was largely genetic in origin, suggesting substantial unique sharing of biological mechanisms between disorders. In contrast, the correlation between ADHD and the externalising-specific factor was much smaller and was largely explained by non-shared environmental effects.…”

“…[5][6][7] A recent meta-analysis of twin studies, however, suggested substantial genetic overlap between ADHD and not only neurodevelopmental disorders, but also externalising and internalising disorders (genetic correlations, 0.49-0.56). 8 These quantitative genetic findings have been paralleled by recent molecular genetic research, further suggesting similar magnitudes of genetic associations between ADHD and neurodevelopmental, externalising and internalising disorders. [9][10][11] The substantial degree of genetic overlap between psychiatric disorders demonstrates that genetic variants that contribute to risk for developing psychiatric disorders have highly pleiotropic effects, i.e.…”

Genetically Informed Regression Analysis: Application to Aggression Prediction by Inattention and Hyperactivity in Children and Adults

“…Hur (2015) presented a review of twin studies on hyperactivity/inattention and Conduct Problems, which showed moderate to high (0.17-0.68) phenotypic correlations, and high genetic correlations (0.43-1.0). Based on a systematic review, Andersson et al (2020) reported a genetic correlation between externalizing symptoms and ADHD of 0.49 (CI 0.37-0.61). These findings are consistent with the substantial genetic correlation between aggression and ADHD (rg = 1.00, SE = 0.07) that was estimated in a recent meta-analysis of genome-wide association studies of childhood aggression and ADHD (Ip et al 2019).…”