Psychiatric disorders in children with 16p11.2 deletion and duplication

Abstract

Deletion and duplication of 16p11.2 (BP4–BP5) have been associated with an increased risk of intellectual disability and psychiatric disorder. This is the first study to compare the frequency of a broad spectrum of psychiatric disorders in children with 16p11.2 deletion and duplication. We aimed to evaluate (1) the nature and prevalence of psychopathology associated with copy number variation (CNV) in children with 16p11.2 by comparing deletion and duplication carriers with family controls; (2) whether deletion and duplication carriers differ in frequency of psychopathology. 217 deletion carriers, 77 deletion family controls, 114 duplication carriers, and 32 duplication family controls participated in the study. Measures included standardized research diagnostic instruments. Deletion carriers had a higher frequency of any psychiatric disorder (OR = 8.9, p < 0.001), attention deficit hyperactivity disorder (ADHD) (OR = 4.0, p = 0.01), and autism spectrum disorder (ASD) (OR = 39.9, p = 0.01) than controls. Duplication carriers had a higher frequency of any psychiatric diagnosis (OR = 5.3, p = 0.01) and ADHD (OR = 7.0, p = 0.02) than controls. The prevalence of ASD in child carriers of deletions and duplications was similar (22% versus 26%). Comparison of the two CNV groups indicated a higher frequency of ADHD in children with the duplication than deletion (OR = 2.7, p = 0.04) as well as a higher frequency of overall psychiatric disorders (OR = 2.8, p = 0.02) and psychotic symptoms (OR = 4.7, p = 0.02). However, no differences between deletion and duplications carriers in the prevalence of ASD were found. Both deletion and duplication are associated with an increased risk of psychiatric disorder, supporting the importance of early recognition, diagnosis, and intervention in these groups.

Psychotic symptoms in 16p11.2 copy‐number variant carriers

“…Although this conflicts with reports of SCZ diagnosis in association with 16p11.2 deletion carriers [Marshall et al, ; Kushima et al, ], we may have been underpowered to detect an association. Only four deletion carriers had psychotic symptoms in our sample, compared with 12 duplication carriers, which is consistent with recent evidence suggesting that psychotic symptoms may be less common in 16p11.2 deletion than duplication carriers [Niarchou et al, ].…”

“…In particular, both 16p11.2 deletion and duplication are associated with autism spectrum disorder (ASD; Weiss et al, ) and schizophrenia (SCZ; McCarthy et al, ; Marshall, Howrigan, Merico, et al, ; Kushima et al, ). ASD prevalence is thought to be similar in both groups, with SCZ symptoms more common in duplication than deletion carriers [Niarchou et al, ].…”

The Role of Genetic Variation of BMI, Body Composition, and Fat Distribution for Mental Traits and Disorders: A Look-Up and Mendelian Randomization Study

“…(3) At the locus 16p.11.2 (see locus 26 in Table 1) higher BMI, BF%, WC, HC, HC adjBMI , and higher risk for obesity were negatively associated with intelligence and educational attainment in line with previous evidence (Jacquemont et al, 2011). Genetic variations [SNPs, copy number variants (CNVs), and larger deletions/insertions] at 16p.11.2 have been shown to be associated with developmental delay, ASD, ADHD, schizophrenia, BD, epilepsy, intracranial volume, brain development, congenital anomalies, altered satiety response, energy imbalance, underweight, and morbid obesity (McCarthy et al, 2009;Bochukova et al, 2010;Fernandez et al, 2010;Walters et al, 2010;Jacquemont et al, 2011;Volckmar et al, 2012;Zufferey et al, 2012;Egger et al, 2014;Qureshi et al, 2014;Volckmar et al, 2015;Maillard et al, 2016;Giuranna et al, 2018;Martin-Brevet et al, 2018;Sonderby et al, 2018;Niarchou et al, 2019). The consequences of 16p11.2 CNV and larger deletions and duplications on health are broad (Crawford et al, 2019;Niarchou et al, 2019).…”

“…Genetic variations [SNPs, copy number variants (CNVs), and larger deletions/insertions] at 16p.11.2 have been shown to be associated with developmental delay, ASD, ADHD, schizophrenia, BD, epilepsy, intracranial volume, brain development, congenital anomalies, altered satiety response, energy imbalance, underweight, and morbid obesity (McCarthy et al, 2009;Bochukova et al, 2010;Fernandez et al, 2010;Walters et al, 2010;Jacquemont et al, 2011;Volckmar et al, 2012;Zufferey et al, 2012;Egger et al, 2014;Qureshi et al, 2014;Volckmar et al, 2015;Maillard et al, 2016;Giuranna et al, 2018;Martin-Brevet et al, 2018;Sonderby et al, 2018;Niarchou et al, 2019). The consequences of 16p11.2 CNV and larger deletions and duplications on health are broad (Crawford et al, 2019;Niarchou et al, 2019). Because the CNVs are rare (Stefansson et al, 2014), large studies and complex analytical methods are needed to detect them in GWAS (Nothen et al, 2019).…”

Neuropsychiatric copy number variants exert shared effects on human brain structure

“…The largest increases in risk for SZ have been documented for the 22q11.2 deletion (30 to 40-fold) followed by the 16p11.2 duplication (10-fold), the 1q21.1 deletion and the 15q11.2 deletion (1.5-fold) 2 . ASD risk is highest for 16p11.2 deletions and duplications (10-fold) followed by 1q21.1 duplications and 22q11.2 duplications (3 to 4-fold) 1,2,[8][9][10][11] . These variants are therefore opportunities to investigate the brain phenotypes associated with high-risk for mental illness.…”