TY - JOUR
T1 - Genetic basis of psychopathological dimensions shared between schizophrenia and bipolar disorder
AU - Corponi, Filippo
AU - Bonassi, Stefano
AU - Vieta, Eduard
AU - Albani, Diego
AU - Serretti, Alessandro
AU - Ducci, Giuseppe
AU - Landi, Stefano
AU - Boccia, Stefania
AU - Serretti, Alessandro
AU - Fabbri, Chiara
PY - 2018
Y1 - 2018
N2 - Shared genetic vulnerability between schizophrenia (SCZ) and bipolar disorder (BP) was demonstrated, but the genetic underpinnings of specific symptom domains are unclear. This study investigated which genes and gene sets may modulate specific psychopathological domains and if genome-wide significant loci previously associated with SCZ or BP may play a role. Genome-wide data were available in patients with SCZ (n = 226) or BP (n = 228). Phenotypes under investigation were depressive and positive symptoms severity, suicidal ideation, onset age and substance use disorder comorbidity. Genome-wide analyses were performed at gene and gene set level, while 148 genome-wide significant loci previously associated with SCZ and/or BP were investigated. Each sample was analyzed separately then a meta-analysis was performed. SH3GL2 and CLVS1 genes were associated with suicidal ideation in SCZ (p = 5.62e-08 and 0.01, respectively), the former also in the meta-analysis (p =.01). SHC4 gene was associated with depressive symptoms severity in BP (p =.003). A gene set involved in cellular differentiation (GO:0048661) was associated with substance disorder comorbidity in the meta-analysis (p =.03). Individual loci previously associated with SCZ or BP did not modulate the phenotypes of interest. This study provided confirmatory and new findings. SH3GL2 (endophilin A1) showed a role in suicidal ideation that may be due to its relevance to the glutamate system. SHC4 regulates BDNF-induced MAPK activation and was previously associated with depression. CLVS1 is involved in lysosome maturation and was for the first time associated with a psychiatric trait. GO:0048661 may mediate the risk of substance disorder through an effect on neurodevelopment/neuroplasticity.
AB - Shared genetic vulnerability between schizophrenia (SCZ) and bipolar disorder (BP) was demonstrated, but the genetic underpinnings of specific symptom domains are unclear. This study investigated which genes and gene sets may modulate specific psychopathological domains and if genome-wide significant loci previously associated with SCZ or BP may play a role. Genome-wide data were available in patients with SCZ (n = 226) or BP (n = 228). Phenotypes under investigation were depressive and positive symptoms severity, suicidal ideation, onset age and substance use disorder comorbidity. Genome-wide analyses were performed at gene and gene set level, while 148 genome-wide significant loci previously associated with SCZ and/or BP were investigated. Each sample was analyzed separately then a meta-analysis was performed. SH3GL2 and CLVS1 genes were associated with suicidal ideation in SCZ (p = 5.62e-08 and 0.01, respectively), the former also in the meta-analysis (p =.01). SHC4 gene was associated with depressive symptoms severity in BP (p =.003). A gene set involved in cellular differentiation (GO:0048661) was associated with substance disorder comorbidity in the meta-analysis (p =.03). Individual loci previously associated with SCZ or BP did not modulate the phenotypes of interest. This study provided confirmatory and new findings. SH3GL2 (endophilin A1) showed a role in suicidal ideation that may be due to its relevance to the glutamate system. SHC4 regulates BDNF-induced MAPK activation and was previously associated with depression. CLVS1 is involved in lysosome maturation and was for the first time associated with a psychiatric trait. GO:0048661 may mediate the risk of substance disorder through an effect on neurodevelopment/neuroplasticity.
KW - Bipolar disorder
KW - Cross-disorder
KW - Gene
KW - Genetics
KW - Pathway
KW - Schizophrenia
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U2 - 10.1016/j.pnpbp.2018.08.023
DO - 10.1016/j.pnpbp.2018.08.023
M3 - Article
C2 - 30149091
AN - SCOPUS:85052451828
VL - 89
SP - 23
EP - 29
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
ER -