Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders
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 perineuron...
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| Published in: | Molecular psychiatry Vol. 16; no. 4; pp. 452 - 461 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
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01-04-2011
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| Abstract | 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. |
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| AbstractList | 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 [gamma]-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 calbindinpositive 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. 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 [gamma]-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 calbindinpositive 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. Molecular Psychiatry (2011) 16, 452-461; doi: 10.1038/mp.2010.23; published online 23 March 2010 Keywords: GABAergic neuron; oligodendrocyte; SNP; expression profile; schizophrenia; bipolar disorder 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. 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. 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 gamma -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. |
| Audience | Academic |
| Author | Kim, S Webster, M J |
| Author_xml | – sequence: 1 givenname: S surname: Kim fullname: Kim, S email: kims@stanleyresearch.org organization: Stanley Brain Research Laboratory, Stanley Medical Research Institute – sequence: 2 givenname: M J surname: Webster fullname: Webster, M J organization: Stanley Brain Research Laboratory, Stanley Medical Research Institute |
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| Keywords | 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 |
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437 EF Torrey (BFmp201023_CR13) 2000; 44 S Purcell (BFmp201023_CR14) 2007; 81 NA Uranova (BFmp201023_CR36) 2007; 10 AJ Myers (BFmp201023_CR8) 2007; 39 BE Stranger (BFmp201023_CR9) 2007; 39 B Short (BFmp201023_CR27) 2001; 155 S Ozawa (BFmp201023_CR29) 1998; 54 AK Stout (BFmp201023_CR30) 1998; 1 VM Vostrikov (BFmp201023_CR2) 2007; 94 M Melone (BFmp201023_CR28) 2004; 14 WJ Gauderman (BFmp201023_CR23) 2002; 155 S Kim (BFmp201023_CR3) 2010; 15 N Uranova (BFmp201023_CR5) 2001; 55 R Karadottir (BFmp201023_CR32) 2005; 438 P Preece (BFmp201023_CR21) 2003; 118 GD Rosen (BFmp201023_CR6) 2001; 2 PM Mangahas (BFmp201023_CR26) 2008; 180 CJ Carter (BFmp201023_CR37) 2007; 33 MR Duchen (BFmp201023_CR31) 2000; 529 MG Salter (BFmp201023_CR33) 2005; 438 S Kim (BFmp201023_CR11) 2007; 8 WE Johnson (BFmp201023_CR20) 2007; 8 Y Hakak (BFmp201023_CR38) 2001; 98 AL Dixon (BFmp201023_CR7) 2007; 39 SJ Huffaker (BFmp201023_CR42) 2009; 15 JW McDonald (BFmp201023_CR34) 1998; 4 D Tkachev (BFmp201023_CR40) 2003; 362 M Borsotto (BFmp201023_CR35) 2007; 7 BW Higgs (BFmp201023_CR12) 2006; 7 RS Spielman (BFmp201023_CR22) 2007; 39 JC Barrett (BFmp201023_CR15) 2005; 21 J Flint (BFmp201023_CR25) 2003; 54 |
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| Snippet | Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic... |
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| Title | Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders |
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