Genetic and environmental contributions to the association between ADHD and affective problems in early childhood—A Swedish population‐based twin study

Rydell, Mina; Taylor, Mark J.; Larsson, Henrik

doi:10.1002/ajmg.b.32536

Cited by 16 publications

(18 citation statements)

References 52 publications

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“…Family studies that studied the association between ADHD and depression suggest that the cooccurrence is influenced by shared familial factors [54,55]. Twin studies of this issue suggest that shared genetic factors explain the overlap of ADHD with depression, anxiety, and internalizing symptoms [56][57][58][59][60]. For example, Cole et al [59].…”

Section: Psychiatric Comorbiditymentioning

confidence: 99%

Genetics of attention deficit hyperactivity disorder

2018

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Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.Attention deficit hyperactivity disorder (ADHD) is a childhood-onset condition with impairing symptoms of inattention, impulsivity, and hyperactivity. Decades of research have documented and replicated key facts about the disorder (for a review, see ref.[1]). It occurs in about 5% of children with little geographic or cross-cultural variation in prevalence and often co-occurs with other conditions, including mood, anxiety, conduct, learning, and substance use disorders. Longitudinal studies show that two-thirds of ADHD youth will continue to have impairing symptoms of ADHD in adulthood. People with ADHD are at risk for a wide range of functional impairments: school failure, peer rejection, injuries due to accidents, criminal behavior, occupational failure, divorce, suicide, and premature death. Although many details of ADHD's pathophysiology are unknown, neuropsychological and neuroimaging studies implicate brain circuits regulating executive functioning, reward processing, timing, and temporal information processing.This article reviews data about the role that genes play in the etiology of ADHD from two perspectives. Family, twin, and adoption studies provide a firm foundation for asserting that genes are involved in the etiology of ADHD. The view from molecular genetics provides a basis for understanding mechanisms whereby genes affect biological pathways that lead to ADHD. Family, twin and adoption studies of ADHDEvidence for heritability from family, adoption, and twin studies A study of 894 ADHD probands and 1135 of their siblings aged 5-17 years old found a ninefold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls [2]. Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors [3,4] with the most recent one reporting rates of ADHD to be greater among biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children. The adoptive relatives had a risk for ADHD like the risk in relatives of control childr...

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Section: Psychiatric Comorbiditymentioning

confidence: 99%

Genetics of attention deficit hyperactivity disorder

2018

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“…For example, twin studies find that early-onset-neurodevelopmental disorders share genetic risk with anxiety (Hallett et al 2010 ; Michelini et al 2015 ; Chen et al 2016 ), MDD (Cole et al 2009 ; Lundström et al 2011 ), affective problems (Rydell et al . 2017 ), and OCD (Pinto et al 2016 ). In a study of specific intellectual domains, problems with communication shared a modest degree of genetic risk with adolescent hallucinations and mania (Cederlöf et al 2014 b ).…”

Section: Shared Genetic Risks Across Child- and Adult-onset Disordersmentioning

confidence: 99%

Assessing the evidence for shared genetic risks across psychiatric disorders and traits

2017

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Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.

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“…31 Secondly, we only included neurodevelopmental and externalizing traits, as both are early onset psychopathology dimensions that are strongly linked to ADHD. Nonetheless, there is also evidence that ADHD in childhood is linked to internalizing traits 28,61 and genomic studies have reported genetic associations across clinical ADHD and depression. 10,43 Future studies assessing genetic specificity and generality in relation to ADHD should therefore aim to also include internalizing traits.…”

Section: Limitationsmentioning

confidence: 99%

The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology

Brikell

Larsson

et al. 2017

Preprint

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Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder, with common genetic risk variants implicated in the clinical diagnosis and symptoms of ADHD.However, given evidence of comorbidity and genetic overlap across neurodevelopmental and externalizing conditions, it remains unclear whether these genetic risk variants are ADHDspecific. The aim of this study was to evaluate the associations between ADHD genetic risks and related neurodevelopmental and externalizing conditions, and to quantify the extent to which any such associations can be attributed to a general genetic liability towards psychopathology. We derived ADHD polygenic risk scores (PRS) for 13,460 children aged 9 and 12 years from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. Associations between ADHD PRS, a latent general psychopathology factor, and six latent neurodevelopmental and externalizing factors were estimated using structural equation modelling. ADHD PRS were statistically significantly associated with elevated levels of inattention, hyperactivity/impulsivity, autistic traits, learning difficulties, oppositional-defiant, and conduct problems (standardized regression coefficients=0.07-0.12). Only the association with specific hyperactivity/impulsivity remained significant after accounting for a general psychopathology factor, on which all symptoms loaded positively (standardized mean loading=0.61, range=0.32-0.91). ADHD PRS simultaneously explained 1% (p-value<0.001) of the variance in the general psychopathology factor and 0.50% (p-value<0.001) in the specific hyperactivity/impulsivity factor. Our results suggest that common genetic risk variants associated with ADHD have largely general pleiotropic effects on neurodevelopmental and externalizing traits in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.

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Genetic and environmental contributions to the association between ADHD and affective problems in early childhood—A Swedish population‐based twin study

Cited by 16 publications

References 52 publications

Genetics of attention deficit hyperactivity disorder

Genetics of attention deficit hyperactivity disorder

Assessing the evidence for shared genetic risks across psychiatric disorders and traits

The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology

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