Genome‐wide analyses of aggressiveness in attention‐deficit hyperactivity disorder

Brevik, Erlend Joramo; Donkelaar, Marjolein M. J. Van; Weber, Heike; Sánchez-Mora, Cristina; Jacob, Christian; Rivero, Olga; Kittel‐Schneider, Sarah; Garcia-Martínez, Iris; Aebi, Marcel; Hulzen, Kimm van; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Lesch, Klaus‐Peter; Reif, Andreas; Ribasés, Marta; Franke, Barbara; Posserud, Maj-Britt; Johansson, Stefan; Lundervold, Astri J.; Haavik, Jan; Zayats, Tetyana

doi:10.1002/ajmg.b.32434

Cited by 41 publications

(32 citation statements)

References 79 publications

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“…For example, one such study conducted a GWAS of conduct disorder symptoms in a population of individuals with comorbid ADHD (Anney et al, 2008). Similar studies have been conducted looking at symptoms of oppositional defiant disorder in individuals with comorbid ADHD (Aebi et al, 2015) and aggressive behavior in individuals with comorbid ADHD (Brevik et al, 2016). Each of the described studies, however, failed to identify any genome-wide significant results, highlighting an important limitation of this approach.…”

Section: Methods For Identifying Individual Variants Related To Multimentioning

confidence: 86%

Molecular genetic approaches to understanding the comorbidity of psychiatric disorders

Gizer

2016

Dev Psychopathol

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Epidemiologic studies demonstrating high rates of co-occurrence among psychiatric disorders at the population level have contributed to large literatures focused on identifying the causal mechanisms underlying the patterns of co-occurrence among these disorders. Such efforts have long represented a core focus of developmental psychopathologists and have more recently been supported by the Research Domain Criteria (RDoC) initiative developed by the National Institute of Mental Health (NIMH), which provides a further framework for how the hypothesized mechanisms can be studied at different levels of analysis. The present overview focuses on molecular genetic approaches that are being used currently to study the etiology of psychiatric disorders, and how these approaches have been applied in efforts to understand the biological mechanisms that give rise to comorbid conditions. The present report begins with a review of molecular genetic approaches used to identify individual variants that confer risk for multiple disorders and the intervening biological mechanisms that contribute to their comorbidity. This is followed by a review of molecular genetic approaches that use genetic data in aggregate to examine these questions, and concludes with a discussion of how developmental psychopathologists are uniquely positioned to apply these methods in a way that will further our understanding of the causal factors that contribute to the development of comorbid conditions.

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Section: Methods For Identifying Individual Variants Related To Multimentioning

confidence: 86%

Molecular genetic approaches to understanding the comorbidity of psychiatric disorders

Gizer

2016

Dev Psychopathol

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“…Our in silico examination of rs17800861 in HaploReg suggests that this SNP is located within active chromatin in the hippocampus, where neurogenesis might be affected by the mode of delivery (Seli & Horvath, ). Moreover, HaploReg also predicted that this SNP may alter the binding of NF‐kappaB factor that has been implicated in several cognition‐related phenotypes, including autism (Naik et al, ), schizophrenia (Song, Lv, Li, Hao, & Zhao, ), aggression (Brevik et al, ), and intellectual disability (Philippe et al, ). Interestingly, VD also correlates with increased activity of NF‐kappaB (Lee et al, ) and may modulate its expression (Cindrova‐Davies et al, ; Li & Karin, ).…”

Section: Discussionmentioning

confidence: 99%

Moderating effect of mode of delivery on the genetics of intelligence: Explorative genome‐wide analyses in ALSPAC

et al. 2018

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IntroductionIntelligence is a core construct of individual differences in cognitive abilities and a strong predictor of important life outcomes. Within recent years, rates of cesarean section have substantially increased globally, though little is known about its effect on neurodevelopmental trajectories. Thus, we aimed to investigate the influence of delivery by cesarean section on the genetics of intelligence in children.MethodsParticipants were recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC). Intelligence was measured by the Wechsler Intelligence Scale for Children (WISC). Genotyping was performed using the Illumina Human Hap 550 quad genome‐wide SNP genotyping platform and was followed by imputation using MACH software. Genome‐wide interaction analyses were conducted using linear regression.ResultsA total of 2,421 children and 2,141,747 SNPs were subjected to the genome‐wide interaction analyses. No variant reached genome‐wide significance. The strongest interaction was observed at rs17800861 in the GRIN2A gene (β = −3.43, 95% CI = −4.74 to −2.12, p = 2.98E−07). This variant is predicted to be located within active chromatin compartments in the hippocampus and may influence binding of the NF‐kappaB transcription factor.ConclusionsOur results may indicate that mode of delivery might have a moderating effect on genetic disposition of intelligence in children. Studies of considerable sizes (>10,000) are likely required to more robustly detect variants governing such interaction. In summary, the presented findings prompt the need for further studies aimed at increasing our understanding of effects various modes of delivery may have on health outcomes in children.

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“…Mutations in the WDR62 can cause severe cerebral cortical abnormalities, including microcephaly, cerebral gyrus hypertrophy with cortical thickening and dysplasia of corpus callosum [6,8,9], all inherited in an autosomal recessive. A number of neurobehavioral abnormalities have been reported, including psychomotor developmental delay, seizure, aggression and irritability [9][10][11]. In addition, some case reports claimed that WDR62 mutation can also cause skin changes [12].…”

Section: Case Presentationmentioning

confidence: 99%

A case report of microcephaly and refractory West syndrome associated with WDR62 mutation

Zhou

Ding

Zeng

et al. 2020

Acta Epileptologica

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The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder characterized by microcephaly with variable degree of intellectual disability. WDR62 has been reported as the second causative gene of MCPH2. West syndrome is a severe epilepsy syndrome composed of the triad of spasms, hypsarrhythmia, and mental retardation. There are limited clinical reports regarding WDR62 mutation and West syndrome. Here we report a boy who was identified with WDR62 mutation and was followed up from age 3 months to 5 months and 14 days. He had the first seizure as the classic epileptic spasm at the age of 3 months. Psychomotor retardation was noted before the seizure occurred. The head circumference was 38.5 cm (SD 2.6) when he was 4 months old, no dysmorphic facial features were observed. He couldn't support his head steadily or turn over. He was able to laugh when tricked by the parents, but couldn't track the sound and light. At the early stage, the electroencephalogram showed multifocal discharges, which evolved into hypsarrhythmia one month later, and brain MRI showed developmental malformation of cerebral gyrus. Two heterozygous mutations were identified in WDR62 by whole exome sequencing c.1535G > A, p.R512Q and c.2618dupT, p.K874Qfs*40. The patient was administrated with oral sodium valproate, nitrazepam, intramuscular adrenocorticotropic hormone for 2 weeks, and followed by prednisone, levetiracetam, topiramate and vigabatrin. However, there was no significant improvement on the seizure control after these treatments. According to the genetic report and clinical manifestation, we speculated that the WDR62 compound heterozygous mutation is responsible for the serious clinical phenotype.

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Genome‐wide analyses of aggressiveness in attention‐deficit hyperactivity disorder

Cited by 41 publications

References 79 publications

Molecular genetic approaches to understanding the comorbidity of psychiatric disorders

Molecular genetic approaches to understanding the comorbidity of psychiatric disorders

Moderating effect of mode of delivery on the genetics of intelligence: Explorative genome‐wide analyses in ALSPAC

A case report of microcephaly and refractory West syndrome associated with WDR62 mutation

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