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...
Published in: | JAMA Psychiatry |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
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2020
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Online Access: | https://research.vumc.nl/en/publications/4129bccf-3b8f-4adf-ac21-ac1486086d40 https://doi.org/10.1001/jamapsychiatry.2019.3779 http://www.scopus.com/inward/record.url?scp=85074651799&partnerID=8YFLogxK |
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Research portal Amsterdam UMC (Vrije Universiteit Amsterdam, Universitair Medische Centra) |
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English |
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, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. Results: Of 45756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23754 (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 carriers ... |
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Article in Journal/Newspaper |
author |
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 Haavik, Jan Haberg, Asta K. Hashimoto, Ryota Hehir-Kwa, Jayne Y. Hibar, Derrek P. Hillegers, Manon H. J. Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Hulshoff Pol, Hilleke E. Ikeda, Masashi Jacquemont, S. bastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G. Kikuchi, Masataka Knowles, Emma E. M. Kwok, John B. le Hellard, Stephanie Linden, David E. J. Liu, Jingyu Lundervold, Arvid Lundervold, Astri J. Martin, Nicholas G. Mather, Karen A. Mathias, Samuel R. McMahon, Katie L. McRae, Allan F. Medland, Sarah E. Moberget, Torgeir Moreau, Clara Morris, Derek W. Mühleisen, Thomas W. Murray, Robin M. Nordvik, Jan E. Nyberg, Lars Olde Loohuis, Loes M. Ophoff, Roel A. Owen, Michael J. Paus, Tomas Pausova, Zdenka Peralta, Juan M. Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, C. line S. Reis Marques, Tiago Rucker, James J. H. Sachdev, Perminder S. Sando, Sigrid B. Schofield, Peter R. Schork, Andrew J. Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I. Sisodiya, Sanjay M. Steen, Vidar M. Stein, Dan J. Strike, Lachlan T. Tamnes, Christian K. Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö. van 't Ent, Dennis van den Bree, Marianne B. M. Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J. Zayats, Tetyana Dale, Anders M. Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T. Stefánsson, Hreinn Stefánsson, K. ri Thompson, Paul M. Andreassen, Ole A. |
spellingShingle |
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 Haavik, Jan Haberg, Asta K. Hashimoto, Ryota Hehir-Kwa, Jayne Y. Hibar, Derrek P. Hillegers, Manon H. J. Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Hulshoff Pol, Hilleke E. Ikeda, Masashi Jacquemont, S. bastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G. Kikuchi, Masataka Knowles, Emma E. M. Kwok, John B. le Hellard, Stephanie Linden, David E. J. Liu, Jingyu Lundervold, Arvid Lundervold, Astri J. Martin, Nicholas G. Mather, Karen A. Mathias, Samuel R. McMahon, Katie L. McRae, Allan F. Medland, Sarah E. Moberget, Torgeir Moreau, Clara Morris, Derek W. Mühleisen, Thomas W. Murray, Robin M. Nordvik, Jan E. Nyberg, Lars Olde Loohuis, Loes M. Ophoff, Roel A. Owen, Michael J. Paus, Tomas Pausova, Zdenka Peralta, Juan M. Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, C. line S. Reis Marques, Tiago Rucker, James J. H. Sachdev, Perminder S. Sando, Sigrid B. Schofield, Peter R. Schork, Andrew J. Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I. Sisodiya, Sanjay M. Steen, Vidar M. Stein, Dan J. Strike, Lachlan T. Tamnes, Christian K. Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö. van 't Ent, Dennis van den Bree, Marianne B. M. Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J. Zayats, Tetyana Dale, Anders M. Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T. Stefánsson, Hreinn Stefánsson, K. ri Thompson, Paul M. Andreassen, Ole A. Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region with Cortical and Subcortical Morphology and Cognition |
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 Haavik, Jan Haberg, Asta K. Hashimoto, Ryota Hehir-Kwa, Jayne Y. Hibar, Derrek P. Hillegers, Manon H. J. Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Hulshoff Pol, Hilleke E. Ikeda, Masashi Jacquemont, S. bastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G. Kikuchi, Masataka Knowles, Emma E. M. Kwok, John B. le Hellard, Stephanie Linden, David E. J. Liu, Jingyu Lundervold, Arvid Lundervold, Astri J. Martin, Nicholas G. Mather, Karen A. Mathias, Samuel R. McMahon, Katie L. McRae, Allan F. Medland, Sarah E. Moberget, Torgeir Moreau, Clara Morris, Derek W. Mühleisen, Thomas W. Murray, Robin M. Nordvik, Jan E. Nyberg, Lars Olde Loohuis, Loes M. Ophoff, Roel A. Owen, Michael J. Paus, Tomas Pausova, Zdenka Peralta, Juan M. Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, C. line S. Reis Marques, Tiago Rucker, James J. H. Sachdev, Perminder S. Sando, Sigrid B. Schofield, Peter R. Schork, Andrew J. Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I. Sisodiya, Sanjay M. Steen, Vidar M. Stein, Dan J. Strike, Lachlan T. Tamnes, Christian K. Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö. van 't Ent, Dennis van den Bree, Marianne B. M. Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J. Zayats, Tetyana Dale, Anders M. Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T. Stefánsson, Hreinn Stefánsson, K. ri Thompson, Paul M. Andreassen, Ole A. |
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 |
publishDate |
2020 |
url |
https://research.vumc.nl/en/publications/4129bccf-3b8f-4adf-ac21-ac1486086d40 https://doi.org/10.1001/jamapsychiatry.2019.3779 http://www.scopus.com/inward/record.url?scp=85074651799&partnerID=8YFLogxK |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
van der Meer , D , Sønderby , I E , Kaufmann , T , Walters , G B , Abdellaoui , A , Ames , D , Amunts , K , Andersson , M , Armstrong , N J , Bernard , M , Blackburn , N B , Blangero , J , Boomsma , D I , Brodaty , H , Brouwer , R M , Bülow , R , Cahn , W , Calhoun , V D , Caspers , S , Cavalleri , G L , Ching , C R K , Cichon , S , Ciufolini , S , Corvin , A , Crespo-Facorro , B , Curran , J E , Dalvie , S , Dazzan , P , de Geus , E J C , de Zubicaray , G I , de Zwarte , S M C , Delanty , N , den Braber , A , Desrivieres , S , di Forti , M , Doherty , J L , Donohoe , G , Ehrlich , S , Eising , E , Espeseth , T , Fisher , S E , Fladby , T , Frei , O , Frouin , V , Fukunaga , M , Gareau , T , Glahn , D C , Grabe , H J , Groenewold , N A , Gústafsson , Ó , Haavik , J , Haberg , A K , Hashimoto , R , Hehir-Kwa , J Y , Hibar , D P , Hillegers , M H J , Hoffmann , P , Holleran , L , Hottenga , J-J , Hulshoff Pol , H E , Ikeda , M , Jacquemont , S B , Jahanshad , N , Jockwitz , C , Johansson , S , Jönsson , E G , Kikuchi , M , Knowles , E E M , Kwok , J B , le Hellard , S , Linden , D E J , Liu , J , Lundervold , A , Lundervold , A J , Martin , N G , Mather , K A , Mathias , S R , McMahon , K L , McRae , A F , Medland , S E , Moberget , T , Moreau , C , Morris , D W , Mühleisen , T W , Murray , R M , Nordvik , J E , Nyberg , L , Olde Loohuis , L M , Ophoff , R A , Owen , M J , Paus , T , Pausova , Z , Peralta , J M , Pike , B , Prieto , C , Quinlan , E B , Reinbold , C L S , Reis Marques , T , Rucker , J J H , Sachdev , P S , Sando , S B , Schofield , P R , Schork , A J , Schumann , G , Shin , J , Shumskaya , E , Silva , A I , Sisodiya , S M , Steen , V M , Stein , D J , Strike , L T , Tamnes , C K , Teumer , A , Thalamuthu , A , Tordesillas-Gutiérrez , D , Uhlmann , A , Úlfarsson , M Ö , van 't Ent , D , van den Bree , M B M , Vassos , E , Wen , W , Wittfeld , K , Wright , M J , Zayats , T , Dale , A M , Djurovic , S , Agartz , I , Westlye , L T , Stefánsson , H , Stefán |
op_relation |
https://research.vumc.nl/en/publications/4129bccf-3b8f-4adf-ac21-ac1486086d40 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1001/jamapsychiatry.2019.3779 |
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JAMA Psychiatry |
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ftvuamsterumc:oai:pure.atira.dk:publications/4129bccf-3b8f-4adf-ac21-ac1486086d40 2024-09-15T18:14:36+00:00 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 Haavik, Jan Haberg, Asta K. Hashimoto, Ryota Hehir-Kwa, Jayne Y. Hibar, Derrek P. Hillegers, Manon H. J. Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Hulshoff Pol, Hilleke E. Ikeda, Masashi Jacquemont, S. bastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G. Kikuchi, Masataka Knowles, Emma E. M. Kwok, John B. le Hellard, Stephanie Linden, David E. J. Liu, Jingyu Lundervold, Arvid Lundervold, Astri J. Martin, Nicholas G. Mather, Karen A. Mathias, Samuel R. McMahon, Katie L. McRae, Allan F. Medland, Sarah E. Moberget, Torgeir Moreau, Clara Morris, Derek W. Mühleisen, Thomas W. Murray, Robin M. Nordvik, Jan E. Nyberg, Lars Olde Loohuis, Loes M. Ophoff, Roel A. Owen, Michael J. Paus, Tomas Pausova, Zdenka Peralta, Juan M. Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, C. line S. Reis Marques, Tiago Rucker, James J. H. Sachdev, Perminder S. Sando, Sigrid B. Schofield, Peter R. Schork, Andrew J. Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I. Sisodiya, Sanjay M. Steen, Vidar M. Stein, Dan J. Strike, Lachlan T. Tamnes, Christian K. Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö. van 't Ent, Dennis van den Bree, Marianne B. M. Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J. Zayats, Tetyana Dale, Anders M. Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T. Stefánsson, Hreinn Stefánsson, K. ri Thompson, Paul M. Andreassen, Ole A. 2020-04-01 https://research.vumc.nl/en/publications/4129bccf-3b8f-4adf-ac21-ac1486086d40 https://doi.org/10.1001/jamapsychiatry.2019.3779 http://www.scopus.com/inward/record.url?scp=85074651799&partnerID=8YFLogxK eng eng https://research.vumc.nl/en/publications/4129bccf-3b8f-4adf-ac21-ac1486086d40 info:eu-repo/semantics/openAccess van der Meer , D , Sønderby , I E , Kaufmann , T , Walters , G B , Abdellaoui , A , Ames , D , Amunts , K , Andersson , M , Armstrong , N J , Bernard , M , Blackburn , N B , Blangero , J , Boomsma , D I , Brodaty , H , Brouwer , R M , Bülow , R , Cahn , W , Calhoun , V D , Caspers , S , Cavalleri , G L , Ching , C R K , Cichon , S , Ciufolini , S , Corvin , A , Crespo-Facorro , B , Curran , J E , Dalvie , S , Dazzan , P , de Geus , E J C , de Zubicaray , G I , de Zwarte , S M C , Delanty , N , den Braber , A , Desrivieres , S , di Forti , M , Doherty , J L , Donohoe , G , Ehrlich , S , Eising , E , Espeseth , T , Fisher , S E , Fladby , T , Frei , O , Frouin , V , Fukunaga , M , Gareau , T , Glahn , D C , Grabe , H J , Groenewold , N A , Gústafsson , Ó , Haavik , J , Haberg , A K , Hashimoto , R , Hehir-Kwa , J Y , Hibar , D P , Hillegers , M H J , Hoffmann , P , Holleran , L , Hottenga , J-J , Hulshoff Pol , H E , Ikeda , M , Jacquemont , S B , Jahanshad , N , Jockwitz , C , Johansson , S , Jönsson , E G , Kikuchi , M , Knowles , E E M , Kwok , J B , le Hellard , S , Linden , D E J , Liu , J , Lundervold , A , Lundervold , A J , Martin , N G , Mather , K A , Mathias , S R , McMahon , K L , McRae , A F , Medland , S E , Moberget , T , Moreau , C , Morris , D W , Mühleisen , T W , Murray , R M , Nordvik , J E , Nyberg , L , Olde Loohuis , L M , Ophoff , R A , Owen , M J , Paus , T , Pausova , Z , Peralta , J M , Pike , B , Prieto , C , Quinlan , E B , Reinbold , C L S , Reis Marques , T , Rucker , J J H , Sachdev , P S , Sando , S B , Schofield , P R , Schork , A J , Schumann , G , Shin , J , Shumskaya , E , Silva , A I , Sisodiya , S M , Steen , V M , Stein , D J , Strike , L T , Tamnes , C K , Teumer , A , Thalamuthu , A , Tordesillas-Gutiérrez , D , Uhlmann , A , Úlfarsson , M Ö , van 't Ent , D , van den Bree , M B M , Vassos , E , Wen , W , Wittfeld , K , Wright , M J , Zayats , T , Dale , A M , Djurovic , S , Agartz , I , Westlye , L T , Stefánsson , H , Stefán article 2020 ftvuamsterumc https://doi.org/10.1001/jamapsychiatry.2019.3779 2024-09-05T01:16:26Z 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, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. Results: Of 45756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23754 (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 carriers ... Article in Journal/Newspaper Iceland Research portal Amsterdam UMC (Vrije Universiteit Amsterdam, Universitair Medische Centra) JAMA Psychiatry 77 4 420 |