Effects of eight neuropsychiatric copy number variants on human brain structure

Claudia Modenato; Kuldeep Kumar; Clara Moreau; Sandra Martin-Brevet; Guillaume Huguet; Catherine Schramm; Martineau Jean-Louis; Charles-Olivier Martin; Nadine Younis; Petra Tamer; Elise Douard; Fanny Thébault-Dagher; Valérie Côté; Audrey-Rose Charlebois; Florence Deguire; Anne Maillard; Borja Rodriguez-Herreros; Aurèlie Pain; Sonia Richetin; Lester Melie-Garcia; Leila Kushan; Ana Silva; Marianne van den Bree; David Linden; Michael Owen; Jeremy Hall; Sarah Lippé; Mallar Chakravarty; Danilo Bzdok; Carrie Bearden; Bogdan Draganski; Sébastien Jacquemont; Marie-Claude Addor; Joris Andrieux; Benoît Arveiler; Geneviève Baujat; Frédérique Sloan-Béna; Marco Belfiore; Dominique Bonneau; Sonia Bouquillon; Odile Boute; Alfredo Brusco; Tiffany Busa; Jean- Hubert Caberg; Dominique Campion; Vanessa Colombert; Marie-Pierre Cordier; Albert David; François-Guillaume Debray; Marie-Ange Delrue; Martine Doco-Fenzy; Ulrike Dunkhase-Heinl; Patrick Edery; Christina Fagerberg; Laurence Faivre; Francesca Forzano; David Genevieve; Marion Gérard; Daniela Giachino; Agnès Guichet; Olivier Guillin; Delphine Héron; Bertrand Isidor; Aurélia Jacquette; Sylvie Jaillard; Hubert Journel; Boris Keren; Didier Lacombe; Sébastien Lebon; Cédric Le Caignec; Marie-Pierre Lemaître; James Lespinasse; Michèle Mathieu-Dramart; Sandra Mercier; Cyril Mignot; Chantal Missirian; Florence Petit; Kristina Pilekær Sørensen; Lucile Pinson; Ghislaine Plessis; Fabienne Prieur; Alexandre Raymond; Caroline Rooryck-Thambo; Massimiliano Rossi; Damien Sanlaville; Britta Schlott Kristiansen; Caroline Schluth-Bolard; Marianne Till; Mieke van Haelst; Lionel van Maldergem; Hanalore Alupay; Benjamin Aaronson; Sean Ackerman; Katy Ankenman; Ayesha Anwar; Constance Atwell; Alexandra Bowe; Arthur Beaudet; Marta Benedetti; Jessica Berg; Jeffrey Berman; Leandra Berry; Audrey Bibb; Lisa Blaskey; Jonathan Brennan; Christie Brewton; Randy Buckner; Polina Bukshpun; Jordan Burko; Phil Cali; Bettina Cerban; Yishin Chang; Maxwell Cheong; Vivian Chow; Zili Chu; Darina Chudnovskaya; Lauren Cornew; Corby Dale; John Dell; Allison Dempsey; Trent Deschamps; Rachel Earl; James Edgar; Jenna Elgin; Jennifer Endre Olson; Yolanda Evans; Anne Findlay; Gerald Fischbach; Charlie Fisk; Brieana Fregeau; Bill Gaetz; Leah Gaetz; Silvia Garza; Jennifer Gerdts; Orit Glenn; Sarah Gobuty; Rachel Golembski; Marion Greenup; Kory Heiken; Katherine Hines; Leighton Hinkley; Frank Jackson; Julian Jenkins; Rita Jeremy; Kelly Johnson; Stephen Kanne; Sudha Kessler; Sarah Khan; Matthew Ku; Emily Kuschner; Anna Laakman; Peter Lam; Morgan Lasala; Hana Lee; Kevin Laguerre; Susan Levy; Alyss Lian Cavanagh; Ashlie Llorens; Katherine Loftus Campe; Tracy Luks; Elysa Marco; Stephen Martin; Alastair Martin; Gabriela Marzano; Christina Masson; Kathleen Mcgovern; Rebecca Mcnally Keehn; David Miller; Fiona Miller; Timothy Moss; Rebecca Murray; Srikantan Nagarajan; Kerri Nowell; Julia Owen; Andrea Paal; Alan Packer; Patricia Page; Brianna Paul; Alana Peters; Danica Peterson; Annapurna Poduri; Nicholas Pojman; Ken Porche; Monica Proud; Saba Qasmieh; Melissa Ramocki; Beau Reilly; Timothy Roberts; Dennis Shaw; Tuhin Sinha; Bethanny Smith-Packard; Anne Snow Gallagher; Vivek Swarnakar; Tony Thieu; Christina Triantafallou; Roger Vaughan; Mari Wakahiro; Arianne Wallace; Tracey Ward; Julia Wenegrat; Anne Wolken

doi:10.1038/s41398-021-01490-9

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Effects of eight neuropsychiatric copy number variants on human brain structure

Journal article

Open access

Peer reviewed

Effects of eight neuropsychiatric copy number variants on human brain structure

Claudia Modenato, Kuldeep Kumar, Clara Moreau, Sandra Martin-Brevet, Guillaume Huguet, Catherine Schramm, Martineau Jean-Louis, Charles-Olivier Martin, Nadine Younis, Petra Tamer, …

Translational Psychiatry, Vol.11(1)

20/07/2021

DOI: https://doi.org/10.1038/s41398-021-01490-9

PMCID: PMC8292542

PMID: 34285187

Abstract

Brain

DNA Copy Number Variations

Humans

Magnetic Resonance Imaging

Neuroimaging

Schizophrenia

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 ( n = 39/28), 16p11.2 ( n = 87/78), 22q11.2 ( n = 75/30), and 15q11.2 ( n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions.

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Title: Effects of eight neuropsychiatric copy number variants on human brain structure
Creators - without role: Claudia Modenato - University of Lausanne
Kuldeep Kumar - Centre Hospitalier Universitaire Sainte-Justine
Clara Moreau - Centre Hospitalier Universitaire Sainte-Justine
Sandra Martin-Brevet - University Hospital of Lausanne
Guillaume Huguet - Centre Hospitalier Universitaire Sainte-Justine
Catherine Schramm - Centre Hospitalier Universitaire Sainte-Justine
Martineau Jean-Louis - Université de Montréal
Charles-Olivier Martin - Centre Hospitalier Universitaire Sainte-Justine
Nadine Younis - Centre Hospitalier Universitaire Sainte-Justine
Petra Tamer - Centre Hospitalier Universitaire Sainte-Justine
Elise Douard - Centre Hospitalier Universitaire Sainte-Justine
Fanny Thébault-Dagher - Centre Hospitalier Universitaire Sainte-Justine
Valérie Côté - Centre Hospitalier Universitaire Sainte-Justine
Audrey-Rose Charlebois - Centre Hospitalier Universitaire Sainte-Justine
Florence Deguire - Centre Hospitalier Universitaire Sainte-Justine
Anne Maillard - University Hospital of Lausanne
Borja Rodriguez-Herreros - University Hospital of Lausanne
Aurèlie Pain - University Hospital of Lausanne
Sonia Richetin - University of Lausanne
Lester Melie-Garcia - École Polytechnique Fédérale de Lausanne
Leila Kushan - University of California [Los Angeles]
Ana Silva - Cardiff University
Marianne van den Bree - Cardiff University
David Linden - Cardiff University
Michael Owen - Cardiff University
Jeremy Hall - Cardiff University
Sarah Lippé - Centre Hospitalier Universitaire Sainte-Justine
Mallar Chakravarty - McGill University
Danilo Bzdok - Montreal Neurological Institute and Hospital
Carrie Bearden - University of California [Los Angeles]
Bogdan Draganski - Max Planck Institute for Human Cognitive and Brain Sciences
Sébastien Jacquemont - Université de Montréal
Marie-Claude Addor
Joris Andrieux - Hôpital Jeanne de Flandre
Benoît Arveiler - Hôpital Pellegrin
Geneviève Baujat - Hôpital Necker-Enfants Malades
Frédérique Sloan-Béna - Hôpital Beau-Séjour
Marco Belfiore - University Hospital of Lausanne
Dominique Bonneau - Centre Hospitalier Universitaire d'Angers
Sonia Bouquillon - Hôpital Jeanne de Flandre
Odile Boute - Centre Hospitalier Universitaire de Lille
Alfredo Brusco - University of Turin
Tiffany Busa - Hôpital de la Timone
Jean- Hubert Caberg - Centre Hospitalier Universitaire de Liège
Dominique Campion - Centre Hospitalier du Rouvray
Vanessa Colombert - Centre hospitalier Bretagne Atlantique
Marie-Pierre Cordier
Albert David - Centre Hospitalier Universitaire de Nantes
François-Guillaume Debray
Marie-Ange Delrue
Martine Doco-Fenzy - Université de Reims Champagne-Ardenne
Ulrike Dunkhase-Heinl - Sygehus Sønderjylland
Patrick Edery - Hospices Civils de Lyon
Christina Fagerberg - Odense University Hospital
Laurence Faivre - Hôpital d'Enfants
Francesca Forzano - Guy's and St Thomas' NHS Foundation Trust
David Genevieve - Université de Montpellier
Marion Gérard - Université de Caen Normandie
Daniela Giachino - University of Turin
Agnès Guichet - Centre Hospitalier Universitaire d'Angers
Olivier Guillin - Centre Hospitalier du Rouvray
Delphine Héron
Bertrand Isidor - Centre Hospitalier Universitaire de Nantes
Aurélia Jacquette - Hôpital Charles-Foix
Sylvie Jaillard - Hôpital Pontchaillou
Hubert Journel - Centre hospitalier Bretagne Atlantique
Boris Keren - Centre de Génétique Moléculaire
Didier Lacombe - Hôpital Pellegrin
Sébastien Lebon - University of Lausanne
Cédric Le Caignec - Centre Hospitalier Universitaire de Nantes
Marie-Pierre Lemaître - Centre Hospitalier Universitaire de Lille
James Lespinasse
Michèle Mathieu-Dramart - Centre Hospitalier Universitaire Amiens-Picardie
Sandra Mercier - Centre Hospitalier Universitaire de Nantes
Cyril Mignot - Sorbonne Université
Chantal Missirian - Hôpital de la Timone
Florence Petit - Centre Hospitalier Universitaire de Lille
Kristina Pilekær Sørensen
Lucile Pinson - Université de Montpellier
Ghislaine Plessis - Centre Hospitalier Universitaire de Caen
Fabienne Prieur - Hôpital Nord
Alexandre Raymond
Caroline Rooryck-Thambo
Massimiliano Rossi - Hospices Civils de Lyon
Damien Sanlaville - Hospices Civils de Lyon
Britta Schlott Kristiansen
Caroline Schluth-Bolard
Marianne Till - Hospices Civils de Lyon
Mieke van Haelst - University Medical Center Utrecht
Lionel van Maldergem - Hôpital Saint-Jacques
Hanalore Alupay - Simons Foundation
Benjamin Aaronson - Simons Foundation
Sean Ackerman - Simons Foundation
Katy Ankenman - Simons Foundation
Ayesha Anwar - Simons Foundation
Constance Atwell - Simons Foundation
Alexandra Bowe - Simons Foundation
Arthur Beaudet - Simons Foundation
Marta Benedetti - Simons Foundation
Jessica Berg - Simons Foundation
Jeffrey Berman - Simons Foundation
Leandra Berry - Simons Foundation
Audrey Bibb - Simons Foundation
Lisa Blaskey - Simons Foundation
Jonathan Brennan - Simons Foundation
Christie Brewton - Simons Foundation
Randy Buckner - Simons Foundation
Polina Bukshpun - Simons Foundation
Jordan Burko - Simons Foundation
Phil Cali - Simons Foundation
Bettina Cerban - Simons Foundation
Yishin Chang
Maxwell Cheong - Simons Foundation
Vivian Chow - Simons Foundation
Zili Chu - Simons Foundation
Darina Chudnovskaya - Simons Foundation
Lauren Cornew - Simons Foundation
Corby Dale - Simons Foundation
John Dell - Simons Foundation
Allison Dempsey - Simons Foundation
Trent Deschamps - Simons Foundation
Rachel Earl - Simons Foundation
James Edgar
Jenna Elgin - Simons Foundation
Jennifer Endre Olson - Simons Foundation
Yolanda Evans - Simons Foundation
Anne Findlay - Simons Foundation
Gerald Fischbach - Simons Foundation
Charlie Fisk
Brieana Fregeau - Simons Foundation
Bill Gaetz - Simons Foundation
Leah Gaetz - Simons Foundation
Silvia Garza - Simons Foundation
Jennifer Gerdts
Orit Glenn - Simons Foundation
Sarah Gobuty - Simons Foundation
Rachel Golembski - Simons Foundation
Marion Greenup - Simons Foundation
Kory Heiken - Simons Foundation
Katherine Hines - Simons Foundation
Leighton Hinkley - Simons Foundation
Frank Jackson - Simons Foundation
Julian Jenkins - Simons Foundation
Rita Jeremy - Simons Foundation
Kelly Johnson - Simons Foundation
Stephen Kanne - Simons Foundation
Sudha Kessler - Simons Foundation
Sarah Khan - Simons Foundation
Matthew Ku - Simons Foundation
Emily Kuschner - Simons Foundation
Anna Laakman - Simons Foundation
Peter Lam - Simons Foundation
Morgan Lasala - Simons Foundation
Hana Lee - Simons Foundation
Kevin Laguerre - Simons Foundation
Susan Levy - Simons Foundation
Alyss Lian Cavanagh - Simons Foundation
Ashlie Llorens - Simons Foundation
Katherine Loftus Campe - Simons Foundation
Tracy Luks - Simons Foundation
Elysa Marco - Simons Foundation
Stephen Martin - Simons Foundation
Alastair Martin - Simons Foundation
Gabriela Marzano - Simons Foundation
Christina Masson - Simons Foundation
Kathleen Mcgovern - Simons Foundation
Rebecca Mcnally Keehn - Simons Foundation
David Miller - Simons Foundation
Fiona Miller - Simons Foundation
Timothy Moss - Simons Foundation
Rebecca Murray - Simons Foundation
Srikantan Nagarajan - Simons Foundation
Kerri Nowell - Simons Foundation
Julia Owen - Simons Foundation
Andrea Paal - Simons Foundation
Alan Packer - Simons Foundation
Patricia Page - Simons Foundation
Brianna Paul - Simons Foundation
Alana Peters - Simons Foundation
Danica Peterson - Simons Foundation
Annapurna Poduri - Simons Foundation
Nicholas Pojman - Simons Foundation
Ken Porche - Simons Foundation
Monica Proud - Simons Foundation
Saba Qasmieh - Simons Foundation
Melissa Ramocki - Simons Foundation
Beau Reilly - Simons Foundation
Timothy Roberts
Dennis Shaw - Simons Foundation
Tuhin Sinha - Simons Foundation
Bethanny Smith-Packard - Simons Foundation
Anne Snow Gallagher - Simons Foundation
Vivek Swarnakar - Simons Foundation
Tony Thieu - Simons Foundation
Christina Triantafallou - Simons Foundation
Roger Vaughan - Simons Foundation
Mari Wakahiro - Simons Foundation
Arianne Wallace - Simons Foundation
Tracey Ward - Simons Foundation
Julia Wenegrat - Simons Foundation
Anne Wolken - Simons Foundation
Publication Details: Translational Psychiatry, Vol.11(1)
Identifiers: 9939946409311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Language: English
Resource Type: Journal article
Local Fields: hal-03652913