Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective

Chronic Stress
Frank R WendtRenato Polimanti

Abstract

Genome-wide association studies (GWAS) have been performed for many psychiatric disorders and revealed a complex polygenic architecture linking mental and physical health phenotypes. Psychiatric diagnoses are often heterogeneous, and several layers of trait heterogeneity may contribute to detection of genetic risks per disorder or across multiple disorders. In this review, we discuss these heterogeneities and their consequences on the discovery of risk loci using large-scale genetic data. We primarily highlight the ways in which sex and diagnostic complexity contribute to risk locus discovery in schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorder, posttraumatic stress disorder, major depressive disorder, obsessive-compulsive disorder, Tourette's syndrome and chronic tic disorder, anxiety disorders, suicidality, feeding and eating disorders, and substance use disorders. Genetic data also have facilitated discovery of clinically relevant subphenotypes also described here. Collectively, GWAS of psychiatric disorders revealed that the understanding of heterogeneity, polygenicity, and pleiotropy is critical to translate genetic findings into treatment strategies.

References

Sep 29, 2000·The American Journal of Psychiatry·P F SullivanK S Kendler
Jun 1, 2002·Trends in Cognitive Sciences·Simon Baron-Cohen
Sep 24, 2005·Health Services Research·Kimberly J O'MalleyCarol M Ashton
Dec 3, 2005·Pediatrics·David S MandellCynthia D Zubritsky
Sep 23, 2006·Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie·Julian M SomersLorena Hsu
Apr 27, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Murray B SteinJoel Gelernter
Jul 4, 2007·Eating Behaviors·Anja Spindler, Gabriella Milos
May 27, 2008·Journal of Psychosomatic Research·Monika MussellBernd Löwe
Jun 17, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Kaixin ZhouStephen V Faraone
Jul 18, 2008·Biological Psychiatry·Xiao-Qing LiuUNKNOWN Autism Genome Project Consortium
Jul 22, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Chloe C Y Wong, Gunter Schumann
Sep 23, 2008·Epidemiologic Reviews·William W EatonPierre Alexandre
Jan 16, 2009·Trends in Genetics : TIG·Nick Craddock, Pamela Sklar
Apr 3, 2009·Annals of the New York Academy of Sciences·Simon Baron-Cohen
Apr 23, 2009·The Journal of Clinical Psychiatry·Larry Culpepper
May 21, 2009·Autism Research : Official Journal of the International Society for Autism Research·Valerie W Hu, Mara E Steinberg
Nov 4, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Simon Baron-CohenEmma Ashwin
Apr 30, 2010·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Alastair J FlintUNKNOWN STOP-PD Study Group
Mar 29, 2011·Journal of Psychiatric Research·Carmen P McLeanStefan G Hofmann
Oct 5, 2011·Archives of General Psychiatry·Merete NordentoftCarsten Bøcker Pedersen
Apr 5, 2012·Molecular Psychiatry·UNKNOWN Major Depressive Disorder Working Group of the Psychiatric GWAS ConsortiumPatrick F Sullivan
Sep 15, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Erik G Willcutt
Oct 18, 2012·Journal of Attention Disorders·Janet K KernRichard C Deth
Dec 27, 2012·Child and Adolescent Psychiatry and Mental Health·Carmen AdornettoSilvia Schneider
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Elise B RobinsonAngelica Ronald
Jun 6, 2013·World Psychiatry : Official Journal of the World Psychiatric Association (WPA)·Darrel A RegierDavid J Kupfer
Jun 28, 2013·Frontiers in Psychiatry·Gricel Orellana, Andrea Slachevsky
Sep 5, 2013·Contemporary Clinical Trials·Sangchoon JeonLawrence Scahill
Dec 4, 2013·Nature Reviews. Neurology·Mary May Robertson
Feb 26, 2014·Schizophrenia Bulletin·Alastair G Cardno, Michael J Owen
Apr 25, 2014·Advances in Wound Care·Donna J Cartwright
May 23, 2014·Schizophrenia Bulletin·Judith M FordBruce N Cuthbert
Jul 25, 2014·Nature·UNKNOWN Schizophrenia Working Group of the Psychiatric Genomics Consortium
Aug 26, 2014·The Psychiatric Clinics of North America·Heidi A BrowneDorothy E Grice
Aug 30, 2014·Psychological Medicine·B VerhulstK S Kendler
Sep 7, 2014·European Psychiatry : the Journal of the Association of European Psychiatrists·D G Lichter, S G Finnegan

❮ Previous
Next ❯

Citations

Nov 28, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Laura Vilar-RibóMaría Soler Artigas
Mar 7, 2021·Journal of Personalized Medicine·Deborah TraversiStefania Boccia
Jul 22, 2021·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Murray B SteinRobert J Ursano

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anxiety Disorders

Discover the latest research on anxiety disorders including agoraphobia, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder here.

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.

Bipolar Disorder

Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.

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.