Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
IMPORTANCE: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent...
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Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096/ http://www.ncbi.nlm.nih.gov/pubmed/31665216 https://doi.org/10.1001/jamapsychiatry.2019.3779 |
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ftpubmed:oai:pubmedcentral.nih.gov:6822096 2023-05-15T16:52:31+02:00 Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition van der Meer, Dennis Sønderby, Ida E. Kaufmann, Tobias Walters, G. Bragi Abdellaoui, Abdel Ames, David Amunts, Katrin Andersson, Micael Armstrong, Nicola J. Bernard, Manon Blackburn, Nicholas B. Blangero, John Boomsma, Dorret I. Brodaty, Henry Brouwer, Rachel M. Bülow, Robin Cahn, Wiepke Calhoun, Vince D. Caspers, Svenja Cavalleri, Gianpiero L. Ching, Christopher R. K. Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E. Dalvie, Shareefa Dazzan, Paola de Geus, Eco J. C. de Zubicaray, Greig I. de Zwarte, Sonja M. C. Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L. Donohoe, Gary Ehrlich, Stefan Eising, Else Espeseth, Thomas Fisher, Simon E. Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C. Grabe, Hans J. Groenewold, Nynke A. Gústafsson, Ómar 2020-04 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096/ http://www.ncbi.nlm.nih.gov/pubmed/31665216 https://doi.org/10.1001/jamapsychiatry.2019.3779 en eng American Medical Association http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096/ http://www.ncbi.nlm.nih.gov/pubmed/31665216 http://dx.doi.org/10.1001/jamapsychiatry.2019.3779 Copyright 2019 American Medical Association. All Rights Reserved. JAMA Psychiatry Original Investigation Text 2020 ftpubmed https://doi.org/10.1001/jamapsychiatry.2019.3779 2020-11-01T01:16:31Z IMPORTANCE: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities. OBJECTIVE: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance. DESIGN, SETTING, AND PARTICIPANTS: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019. MAIN OUTCOMES AND MEASURES: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age(2), sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. RESULTS: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = −0.41; SE, 0.08; P = 4.9 × 10(−8)), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10(−7)), and a smaller nucleus accumbens (Cohen d = −0.27; SE, 0.07; P = 7.3 × 10(−5)). There was also a significant negative dose response on cortical thickness (β = −0.24; SE, 0.05; P = 6.8 × 10(−7)). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion ... Text Iceland PubMed Central (PMC) JAMA Psychiatry 77 4 420 |
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Original Investigation van der Meer, Dennis Sønderby, Ida E. Kaufmann, Tobias Walters, G. Bragi Abdellaoui, Abdel Ames, David Amunts, Katrin Andersson, Micael Armstrong, Nicola J. Bernard, Manon Blackburn, Nicholas B. Blangero, John Boomsma, Dorret I. Brodaty, Henry Brouwer, Rachel M. Bülow, Robin Cahn, Wiepke Calhoun, Vince D. Caspers, Svenja Cavalleri, Gianpiero L. Ching, Christopher R. K. Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E. Dalvie, Shareefa Dazzan, Paola de Geus, Eco J. C. de Zubicaray, Greig I. de Zwarte, Sonja M. C. Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L. Donohoe, Gary Ehrlich, Stefan Eising, Else Espeseth, Thomas Fisher, Simon E. Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C. Grabe, Hans J. Groenewold, Nynke A. Gústafsson, Ómar Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition |
topic_facet |
Original Investigation |
description |
IMPORTANCE: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities. OBJECTIVE: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance. DESIGN, SETTING, AND PARTICIPANTS: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019. MAIN OUTCOMES AND MEASURES: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age(2), sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. RESULTS: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = −0.41; SE, 0.08; P = 4.9 × 10(−8)), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10(−7)), and a smaller nucleus accumbens (Cohen d = −0.27; SE, 0.07; P = 7.3 × 10(−5)). There was also a significant negative dose response on cortical thickness (β = −0.24; SE, 0.05; P = 6.8 × 10(−7)). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion ... |
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van der Meer, Dennis Sønderby, Ida E. Kaufmann, Tobias Walters, G. Bragi Abdellaoui, Abdel Ames, David Amunts, Katrin Andersson, Micael Armstrong, Nicola J. Bernard, Manon Blackburn, Nicholas B. Blangero, John Boomsma, Dorret I. Brodaty, Henry Brouwer, Rachel M. Bülow, Robin Cahn, Wiepke Calhoun, Vince D. Caspers, Svenja Cavalleri, Gianpiero L. Ching, Christopher R. K. Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E. Dalvie, Shareefa Dazzan, Paola de Geus, Eco J. C. de Zubicaray, Greig I. de Zwarte, Sonja M. C. Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L. Donohoe, Gary Ehrlich, Stefan Eising, Else Espeseth, Thomas Fisher, Simon E. Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C. Grabe, Hans J. Groenewold, Nynke A. Gústafsson, Ómar |
author_facet |
van der Meer, Dennis Sønderby, Ida E. Kaufmann, Tobias Walters, G. Bragi Abdellaoui, Abdel Ames, David Amunts, Katrin Andersson, Micael Armstrong, Nicola J. Bernard, Manon Blackburn, Nicholas B. Blangero, John Boomsma, Dorret I. Brodaty, Henry Brouwer, Rachel M. Bülow, Robin Cahn, Wiepke Calhoun, Vince D. Caspers, Svenja Cavalleri, Gianpiero L. Ching, Christopher R. K. Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E. Dalvie, Shareefa Dazzan, Paola de Geus, Eco J. C. de Zubicaray, Greig I. de Zwarte, Sonja M. C. Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L. Donohoe, Gary Ehrlich, Stefan Eising, Else Espeseth, Thomas Fisher, Simon E. Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C. Grabe, Hans J. Groenewold, Nynke A. Gústafsson, Ómar |
author_sort |
van der Meer, Dennis |
title |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition |
title_short |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition |
title_full |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition |
title_fullStr |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition |
title_full_unstemmed |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition |
title_sort |
association of copy number variation of the 15q11.2 bp1-bp2 region with cortical and subcortical morphology and cognition |
publisher |
American Medical Association |
publishDate |
2020 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096/ http://www.ncbi.nlm.nih.gov/pubmed/31665216 https://doi.org/10.1001/jamapsychiatry.2019.3779 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
JAMA Psychiatry |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096/ http://www.ncbi.nlm.nih.gov/pubmed/31665216 http://dx.doi.org/10.1001/jamapsychiatry.2019.3779 |
op_rights |
Copyright 2019 American Medical Association. All Rights Reserved. |
op_doi |
https://doi.org/10.1001/jamapsychiatry.2019.3779 |
container_title |
JAMA Psychiatry |
container_volume |
77 |
container_issue |
4 |
container_start_page |
420 |
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1766042854139887616 |