Increased risk of ADHD in families with ASD

Septier, Mathilde; Peyre, Hugo; Amsellem, Frédérique; Beggiato, Anita; Maruani, Anna; Poumeyreau, Marion; Amestoy, Anouck; Scheid, Isabelle; Gaman, Alexandru; Bolognani, Federico; Honey, Garry D.; Bouquet, Céline; Moal, Myriam Ly‐Le; Bouvard, Manuel; Leboyer, Marion; Bourgeron, Thomas; Delorme, Richard

doi:10.1007/s00787-018-1206-0

Cited by 24 publications

(15 citation statements)

References 54 publications

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“…We found that 44% percent of the SNPs associated with ASD colocalized with ADHD SNPs, and 26% of the SNPs associated with ADHD colocalized with ASD SNPs (at p <1e-6). These results are consistent with the abundant evidence for shared genetic factors in ASD and ADHD from family-based (16,17), twin-based (18,19), and clinical studies on rare genetic variants (20– 22). In addition, results from bidirectional Mendelian randomisation analyses indicated that ASD increased the risk of ADHD and vice versa.…”

Section: Discussionsupporting

confidence: 90%

“…Several lines of evidence also point toward the presence of shared genetic factors in ASD and ADHD. In family-based studies, relatives of children with ASD are at a higher risk for ADHD than relatives of children without ASD (16,17) and in twin studies, researchers report strong genetic correlations between traits related to ADHD and traits related to ASD (18,19). Moreover, a similar burden of rare protein-truncating variants has been found in individuals with ASD and those with ADHD (20).…”

Section: Introductionmentioning

confidence: 99%

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Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHD

Peyre

Schoeler

Liu

et al. 2020

Preprint

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1Background: Several lines of evidence point toward the presence of shared genetic factors 2 underlying Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder 3 (ADHD). However, Genome-Wide Association Studies (GWAS) have yet to identify risk 4 variants (i.e. Single-Nucleotide Polymorphisms, SNPs) shared by ADHD and ASD. 5Methods: Two complementary multivariate analyses -genomic structural equation 6 modelling (SEM) and colocalization analysis -were exploited to identify the shared SNPs for 7 ASD and ADHD, using summary data from two independent GWAS of ASD (N=46,350) 8 and ADHD individuals (N=55,374). 9Results: Genomic SEM identified 7 novel SNPs shared between ASD and ADHD (p genome-10 wide <5e-8), including three SNPs that were not identified in any of the original univariate 11 GWAS of ASD and ADHD (rs227378, rs2391769 and rs325506). We also mapped 4 novel 12 genes (MANBA, DPYD, INSM1, and PAX1) to SNPs shared by ASD and ADHD, as well as 13 4 genes that had already been mapped to SNPs identified in either ASD or ADHD GWAS 14 (SORCS3, XRN2, PTBP2 and NKX2-4). All the shared genes between ADHD and ASD 15 were more prominently expressed in the brain than the genes mapped to SNPs specific to 16 ASD or ADHD. Colocalization analyses revealed that 44% percent of the SNPs associated 17 with ASD (p<1e-6) colocalized with ADHD SNPs and 26% of the SNPs associated with 18 ADHD (p<1e-6) colocalized with ASD SNPs. 19Conclusions: Using multivariate genomic analyses, the present study reveals the shared 20 genetic pathways that underlie ASD and ADHD. Further investigation of these pathways may 21 help identify new targets for treatment of these disorders. 22 23 24 25

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHD

Peyre

Schoeler

Liu

et al. 2020

Preprint

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“…ASD, ADHD, and schizophrenia are all neurodevelopmental disorders characterized by derailed brain development, resulting in brain dysfunction later from childhood to adulthood, sharing vulnerability genes (35), and clinical features (36). It has been shown that the risk of ADHD is higher in ASD families (37) and that ADHD is also the most common comorbidity in autistic patients (38) as well as in the past, ASD has been defined as an early manifestation of schizophrenia since one-third of childhood onset cases received first a diagnosis of ASD (39). From our point of view, these disorders show another common feature regarding altered activity of some HERV families, as demonstrated by our group in peripheral blood mononuclear cells from patients with ASD or ADHD (10–12) and in brain and blood from schizophrenia patients (40, 41).…”

Section: Discussionmentioning

confidence: 99%

Children With Autism Spectrum Disorder and Their Mothers Share Abnormal Expression of Selected Endogenous Retroviruses Families and Cytokines

et al. 2019

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The Autism Spectrum Disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, only clinically diagnosed since the lack of reliable biomarkers. Autism etiology is probably attributable to the combination of genetic vulnerability and environmental factors, and recently, maternal immune activation has been linked to derailed neurodevelopment, resulting in ASD in the offspring. Human endogenous retroviruses (HERVs) are relics of ancestral infections, stably integrated in the human DNA. Given the HERV persistence in the genome, some of HERVs have been co-opted for physiological functions during evolution, while their reactivation has been associated with several pathological conditions, including cancer, autoimmune, and neurological and psychiatric disorders. Particularly, due to their intrinsic responsiveness to external stimuli, HERVs can modulate the host immune response and in turn HERVs can be activated by the immune effectors. In previous works we demonstrated high expression levels of HERV-H in blood of autistic patients, closely related with the severity of the disease. Moreover, in a preclinical ASD model we proved changes of expression of several ERV families and cytokines from the intrauterine life to the adulthood, and across generations via maternal lineage. Here we analyzed the expression of HEMO and of selected HERVs and cytokines in blood from ASD patients and their parents and corresponding healthy controls, to look for a common molecular trait within family members. ASD patients and their mothers share altered expression of HERV-H and HEMO and of cytokines such as TNF-α, IFN-γ, IL-10. The multivariate regression models showed a mother-child association by HEMO activity and demonstrated in children and mothers an association between HERV-H and HEMO expression and, only in mothers, between HEMO, and TNF-α expression. Furthermore, high diagnostic performance for HERV-H and HEMO was found, suggesting their potential application for the identification of ASD children and their mothers. The present data support the involvement of HERVs in ASD and suggest HERVs and cytokines as ASD-associated traits. Since ASD is a heterogeneous group of neurodevelopmental disorders, a single determinant alone could be not enough to account for the complexity, and HERV/cytokines expression could be considered in a set of biomarkers, easily detectable in blood, and potentially useful for an early diagnosis.

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“…Autism and ADHD may share common antecedents of genetic origin, relating to difficulties with attentional control (Visser et al 2016 ). This common genetic link may explain why autism and ADHD cluster in families, such that a child with an autistic first-degree relative is more likely than average to have ADHD, and vice versa (Chien et al 2017 ; Ghirardi et al 2017 ; Miller et al 2019 ; Oerlemans et al 2015 ; Septier et al 2019 ). Thus, in this study we investigate early development of attentional control as a possible intermediate phenotype of autism and ADHD.…”

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confidence: 99%

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

Hendry

Jones

Bedford

et al. 2020

J Autism Dev Disord

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Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals' mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7-9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.

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Increased risk of ADHD in families with ASD

Cited by 24 publications

References 54 publications

Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHD

Combining multivariate genomic approaches to elucidate the comorbidity between ASD and ADHD

Children With Autism Spectrum Disorder and Their Mothers Share Abnormal Expression of Selected Endogenous Retroviruses Families and Cytokines

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

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