Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study

16p11.2 European Consortium

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Resumé

BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.

METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.

RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.

CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.

OriginalsprogEngelsk
TidsskriftBiological Psychiatry
Vol/bind84
Udgave nummer4
Sider (fra-til)253-264
ISSN0006-3223
DOI
StatusUdgivet - 15. aug. 2018

Fingeraftryk

Language
Neuroimaging
Cognition
Meta-Analysis
Power (Psychology)
Cognitive Dysfunction
Autism Spectrum Disorder

Citer dette

@article{e736031ced584a9f835136b23cb6cd16,
title = "Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study",
abstract = "BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.",
keywords = "16p11.2, Autism spectrum disorder, Copy number variant, Genetics, Imaging, Neurodevelopmental disorders",
author = "Sandra Martin-Brevet and Borja Rodr{\'i}guez-Herreros and Nielsen, {Jared A} and Clara Moreau and Claudia Modenato and Maillard, {Anne M} and Aur{\'e}lie Pain and Sonia Richetin and J{\o}nch, {Aia E} and Qureshi, {Abid Y} and Z{\"u}rcher, {Nicole R} and Philippe Conus and Chung, {Wendy K} and Sherr, {Elliott H} and Spiro, {John E} and Ferath Kherif and Beckmann, {Jacques S} and Nouchine Hadjikhani and Alexandre Reymond and Buckner, {Randy L} and Bogdan Draganski and S{\'e}bastien Jacquemont and {16p11.2 European Consortium}",
note = "Copyright {\circledC} 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "8",
day = "15",
doi = "10.1016/j.biopsych.2018.02.1176",
language = "English",
volume = "84",
pages = "253--264",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Heinemann",
number = "4",

}

Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure : A Multisite Genetic-First Study. / 16p11.2 European Consortium.

I: Biological Psychiatry, Bind 84, Nr. 4, 15.08.2018, s. 253-264.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure

T2 - A Multisite Genetic-First Study

AU - Martin-Brevet, Sandra

AU - Rodríguez-Herreros, Borja

AU - Nielsen, Jared A

AU - Moreau, Clara

AU - Modenato, Claudia

AU - Maillard, Anne M

AU - Pain, Aurélie

AU - Richetin, Sonia

AU - Jønch, Aia E

AU - Qureshi, Abid Y

AU - Zürcher, Nicole R

AU - Conus, Philippe

AU - Chung, Wendy K

AU - Sherr, Elliott H

AU - Spiro, John E

AU - Kherif, Ferath

AU - Beckmann, Jacques S

AU - Hadjikhani, Nouchine

AU - Reymond, Alexandre

AU - Buckner, Randy L

AU - Draganski, Bogdan

AU - Jacquemont, Sébastien

AU - 16p11.2 European Consortium

N1 - Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2018/8/15

Y1 - 2018/8/15

N2 - BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.

AB - BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.

KW - 16p11.2

KW - Autism spectrum disorder

KW - Copy number variant

KW - Genetics

KW - Imaging

KW - Neurodevelopmental disorders

U2 - 10.1016/j.biopsych.2018.02.1176

DO - 10.1016/j.biopsych.2018.02.1176

M3 - Journal article

C2 - 29778275

VL - 84

SP - 253

EP - 264

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 4

ER -