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November 13-14, 2019 | London, UK
WORLD CONGRESS ON MENTAL HEALTH
Clin Psychol Cog Sci, Volume 03
Volume 03
Journal of Clinical Psychology and Cognitive Science Mental Health 2019
November 13-14, 2019
Genotype–phenotype associations in children with copy number variants associated
with high neuropsychiatric risk: Case-control analysis of the IMAGINE-ID study data
Statement of the problem: Several genomic disorders caused bymicro-
deletion or duplication of chromosomal material Copy Number Variants
(CNVs) have been associated with high risk of neurodevelopmental and
psychiatric disorder (referred to as ND-CNVs). However, it remains
unclear to what extent the different genotypes lead distinct and specific
patterns of cognitive and behavioural outcomes.
Methodology: Families of 258 children, aged 6–19 years, with at
least one of 13 ND-CNVs across 9 loci (1q21.1 [proximal duplication,
and distal deletion and duplication], 2p16.3 deletion, 9q34.3 deletion,
15q11.2 deletion, 15q13.3 deletion and duplication, 16p11.2 [proximal
deletion and duplication, and distal deletion], and 22q11.2 deletion and
duplication) were recruited via the UK National Health Service (NHS)
medical genetic clinic network and patient support groups as part
of the IMAGINE-ID study. A control sample of 106 siblings of these
index children, who did not have these ND-CNVs also took part. All
children were assessed for psychiatric disorders and broader traits of
neurodevelopmental, cognitive, and psychopathological origin.
Findings: ND-CNV carriers were impaired across all neurodevelopmental, cognitive, and psychopathological traits compared
with controls. 186 (80%) met criteria for one or more psychiatric disorder (OR=13.8, p<.000, compared with controls). Risk of
attention-deficit hyperactivity disorder (OR=6.9, p<.000), oppositional defiant disorder (OR=3.6, p=.012), any anxiety disorder
(OR=2.9, p=.0146), and autism spectrum disorder traits (OR=44.1, p<.000) was particularly high compared with controls.
Only moderate quantitative and qualitative differences in phenotypic profile were found between genotypes. Specific genotype
accounted for a low proportion of variance in cognitive and behavioural outcomes (~5–20% depending on the trait).
Conclusion and significance: These ND-CNVs have a similar range of adverse effects on childhood neurodevelopment, despite
subtle quantitative and qualitative differences. Genomic risk for neuropsychiatric disorder impacts on multiple processes and
neural circuits, indicating that future research should avoid a narrow focus on single phenotypes.
Biography
Marianne B M van den Bree has developed a unique longitudinal research programme of individuals with rare genomic disorders caused by
pathogenic Copy Number Variants (CNVs) that are associated with high risk of neurodevelopmental and psychiatric disorder. Detailed and
wide-ranging phenotypic assessments are conducted on individuals with these neurodevelopmental risk CNVs (ND-CNVs) and their family
members. Her research is elucidating the still poorly understood complex phenotypic presentation of these patients. Her research papers have
documented the rate and nature of the neurodevelopmental, psychiatric, neurological, neurocognitive and sleep problems these patients can
face. Her longitudinal studies of patients with 22q11.2 deletion syndrome (22q11.2DS), which is associated with high risk of schizophrenia,
have contributed to understanding of the childhood predictors of the development of subthreshold psychotic phenomena in adolescence.
Marianne B M van den Bree
Cardiff University, UK
Phenotypic profiles of individual ND-CNV genotypes. Domains are clustered
into two groups; mental health and cognitive comorbidities (cluster A)
and neurodevelopmental traits (cluster B). The lighter colour indicates
a Z score difference of zero between the ND-CNV group and controls, with
darker colours indicating a deficit in the ND-CNV group compared with
the controls. ADHD=attention-deficit hyperactivity disorder. ASD=autism
spectrum disorder. ND-CNV=neuropsychiatric disorder-copy number variant.
OCD=obsessive-compulsive disorder. ODD=oppositional defiant disorder.