Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

• Published in: Molecular psychiatry Vol. 16; no. 4; pp. 452 - 461
• Main Authors: Kim, S, Webster, M J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2011; Nature Publishing Group
• Subjects: 631/208/205; 631/378/1457/1945; 692/699/476; Adult; Adult and adolescent clinical studies; Amino Acid Transport System A - genetics; Apoptosis; Association analysis; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Bipolar disorder; Bipolar disorders; Brain research; Calbindin; Calbindins; Causality; Databases, Genetic; Development and progression; Etiology; Female; gamma-Aminobutyric Acid - genetics; Gene expression; Gene Expression Profiling; Genetic aspects; Genetic Predisposition to Disease; Genetic susceptibility; Genome-Wide Association Study; Genomes; Genotype; Humans; Male; Medical research; Medical sciences; Medicine; Medicine & Public Health; Mental depression; Mental disorders; Mental Disorders - genetics; Mental Disorders - pathology; Middle Aged; Mood disorders; Neurons; Neurosciences; Oligodendrocytes; Oligodendroglia - pathology; Oligonucleotide Array Sequence Analysis; original-article; Pharmacotherapy; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide - genetics; Prefrontal cortex; Prefrontal Cortex - pathology; Protein Phosphatase 2 - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Quality control; rab2 GTP-Binding Protein - genetics; Research centers; Risk factors; S100 Calcium Binding Protein G - genetics; Schizophrenia; Single-nucleotide polymorphism; γ-Aminobutyric acid; United States; United States > US; GABAergic neuron; bipolar disorder; schizophrenia; SNP; expression profile; oligodendrocyte; Mood disorder; Neuroglia; Central nervous system; Schizophrenia; Bipolar disorder; Prefrontal cortex; Encephalon; Psychosis; Oligodendrocyte; Mental disorder; Gabaergic neuron
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2010.23

Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic causalities that may underlie the cytoarchitectural abnormalities of calbindin-containing γ-aminobutyric acid (GABA)ergic neurons and perineuronal oligodendrocytes in the PFC of subjects with psychiatric disorders by converging results from genome-wide single-nucleotide polymorphism (SNP) scans for the traits and expression SNP (eSNP) associations. In the initial genome-wide scans, we identified several development- and apoptosis-related genes associated with the cytoarchitectural traits. Moreover, the susceptibility gene for bipolar disorder,
PPP2R2C
, was found to be associated with the number of perineuronal oligodendrocytes. Further eSNP analyses indicated that two novel candidate genes,
RAB2A
and
SLC38A1,
were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes, respectively. Our findings may provide novel insights into the genetic causalities associated with cytoarchitectural abnormalities in the PFC of subjects with major psychiatric disorders as well as into the etiology of such disorders.