Synaptic and transcriptionally downregulated genes are associated with cortical thickness differences in autism.

Molecular Psychiatry
Rafael Romero-GarciaRichard A I Bethlehem

Abstract

Differences in cortical morphology-in particular, cortical volume, thickness and surface area-have been reported in individuals with autism. However, it is unclear what aspects of genetic and transcriptomic variation are associated with these differences. Here we investigate the genetic correlates of global cortical thickness differences (ΔCT) in children with autism. We used Partial Least Squares Regression (PLSR) on structural MRI data from 548 children (166 with autism, 295 neurotypical children and 87 children with ADHD) and cortical gene expression data from the Allen Institute for Brain Science to identify genetic correlates of ΔCT in autism. We identify that these genes are enriched for synaptic transmission pathways and explain significant variation in ΔCT. These genes are also significantly enriched for genes dysregulated in the autism post-mortem cortex (Odd Ratio (OR) = 1.11, Pcorrected  10-14), driven entirely by downregulated genes (OR = 1.87, Pcorrected  10-15). We validated the enrichment for downregulated genes in two independent data sets: Validation 1 (OR = 1.44, Pcorrected = 0.004) and Validation 2 (OR = 1.30; Pcorrected = 0.001). We conclude that transcriptionally downregulated genes implicated in autism are...Continue Reading

References

Mar 1, 2003·Molecular Psychiatry·L A WeissM H Meisler
Nov 25, 2005·Cerebral Cortex·Nouchine HadjikhaniHelen Tager-Flusberg
Jul 4, 2006·The American Journal of Psychiatry·Antonio Y HardanNancy J Minshew
Mar 21, 2009·Cerebral Cortex·Matthew S PanizzonWilliam S Kremen
May 5, 2009·The Journal of Comparative Neurology·Camilla ButtiPatrick R Hof
Jun 24, 2009·Current Opinion in Neurobiology·Thomas Bourgeron
May 27, 2011·Nature·Irina VoineaguDaniel H Geschwind
Mar 31, 2012·Science·Karl Zilles, Katrin Amunts
Aug 4, 2012·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Lisa T EylerWilliam S Kremen
Sep 22, 2012·Nature·Michael J HawrylyczAllan R Jones
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Jul 31, 2013·Genome Biology·Daniel GlassTim D Spector
Aug 13, 2013·Brain : a Journal of Neurology·Meng-Chuan LaiSimon Baron-Cohen
Sep 18, 2013·Journal of Neurodevelopmental Disorders·Jun WangJohn A Sweeney
Jan 15, 2014·Nature Reviews. Neurology·Christine Ecker, Declan Murphy
Apr 24, 2014·Brain : a Journal of Neurology·Brandon A ZielinskiJanet E Lainhart
Jul 21, 2014·Nature Genetics·Trent GauglerJoseph D Buxbaum
Sep 5, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ye ZhangJian Qian Wu
Oct 16, 2014·Cerebral Cortex·Shlomi HaarIlan Dinstein
Nov 5, 2014·Nature·Silvia De RubeisJoseph D Buxbaum
Nov 11, 2014·Autism Research : Official Journal of the International Society for Autism Research·Nicholas LangeJanet E Lainhart
Jan 22, 2015·Nature·Derrek P HibarSarah E Medland
Mar 1, 2015·NeuroImage·Konrad WagstylPaul C Fletcher
Apr 18, 2015·PLoS Computational Biology·Christiaan A de LeeuwDanielle Posthuma
May 4, 2015·Brain : a Journal of Neurology·Rebecca McKavanaghSteven A Chance
Aug 21, 2015·Nature Reviews. Neuroscience·Thomas Bourgeron
Nov 17, 2015·Nature Neuroscience·Michael HawrylyczEd Lein
Dec 29, 2015·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Beata TickFrühling Rijsdijk
Apr 12, 2016·Human Brain Mapping·Elizabeth SmithArmin Raznahan
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
Jun 13, 2016·Comptes rendus biologies·Thomas Bourgeron
Jul 28, 2016·Proceedings of the National Academy of Sciences of the United States of America·Kirstie J WhitakerEdward T Bullmore
Aug 16, 2016·NPJ Genomic Medicine·Ryan K C YuenStephen W Scherer
Oct 28, 2016·Nature Neuroscience·Menachem FromerPamela Sklar

❮ Previous
Next ❯

Citations

Mar 19, 2020·Cerebral Cortex·Jilian FuUNKNOWN Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Jun 4, 2020·Autism Research : Official Journal of the International Society for Autism Research·Sofia StathopoulosColleen O'Ryan
Aug 12, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Amanda M Buch, Conor Liston
Sep 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kevin M AndersonAvram J Holmes
Apr 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sarah E MorganEdward T Bullmore
Aug 26, 2020·Human Brain Mapping·Qiang XuChunshui Yu
Jul 6, 2020·Nature Communications·Jakob SeidlitzArmin Raznahan
Oct 6, 2020·Autism Research : Official Journal of the International Society for Autism Research·Kaitlyn E May, Rajesh K Kana
Mar 2, 2021·Neurobiology of Stress·Mandy MeijerAhmed Mahfouz
Mar 13, 2021·Biological Psychiatry : Cognitive Neuroscience and Neuroimaging·Gregor GryglewskiRupert Lanzenberger
Jul 20, 2019·Biological Psychiatry·Martijn P van den HeuvelRené S Kahn
Apr 4, 2021·Current Opinion in Genetics & Development·Clara A MoreauCarrie E Bearden
May 7, 2021·Neuropathology and Applied Neurobiology·Antonio Jimenez-MarinJesus M Cortes
Mar 12, 2021·Brain : a Journal of Neurology·George E C ThomasRimona S Weil
Aug 30, 2021·Journal of Neurology·Jie SunChunshui Yu
Sep 11, 2021·The American Journal of Psychiatry·Christine EckerDeclan G M Murphy

❮ Previous
Next ❯

Software Mentioned

Enrichr
freesurfer
BrainsForPublication
MAGMA

Related Concepts

Related Feeds

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.