| Full text | |
| Author(s): Show less - |
Goncalves, Vanessa F.
[1, 2]
;
Cappi, Carolina
[3]
;
Hagen, Christian M.
[4]
;
Sequeira, Adolfo
[5]
;
Vawter, Marquis P.
[5]
;
Derkach, Andriy
[6]
;
Zai, Clement C.
[1, 2]
;
Hedley, Paula L.
[4]
;
Bybjerg-Grauholm, Jonas
[4]
;
Pouget, Jennie G.
[1, 2]
;
Cuperfain, Ari B.
[1, 2]
;
Sullivan, Patrick F.
[7, 8]
;
Christiansen, Michael
[4, 9]
;
Kennedy, James L.
[1, 2]
;
Sun, Lei
[6, 10]
Total Authors: 15
|
| Affiliation: | [1] Univ Toronto, Dalla Lana Sch Publ Hlth, Fac Arts & Sci, Dept Psychiat, Toronto, ON - Canada
[2] Ctr Addict & Mental Hlth, Neurosci Sect, Toronto, ON - Canada
[3] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo - Brazil
[4] Univ Copenhagen, Statens Serum Inst, Dept Congenital Disorders, Copenhagen - Denmark
[5] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 - USA
[6] Univ Toronto, Dalla Lana Sch Publ Hlth, Fac Arts & Sci, Dept Stat Sci, Toronto, ON - Canada
[7] Univ N Carolina, Dept Genet, Chapel Hill, NC - USA
[8] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm - Sweden
[9] Univ Copenhagen, Dept Biomed Sci, Copenhagen - Denmark
[10] Univ Toronto, Dalla Lana Sch Publ Hlth, Biostat Div, Toronto, ON - Canada
Total Affiliations: 10
|
| Document type: | Journal article |
| Source: | BIOLOGICAL PSYCHIATRY; v. 83, n. 9, p. 780-789, MAY 1 2018. |
| Web of Science Citations: | 3 |
| Abstract | |
BACKGROUND: The genetic risk factors of schizophrenia (SCZ), a severe psychiatric disorder, are not yet fully understood. Multiple lines of evidence suggest that mitochondrial dysfunction may play a role in SCZ, but comprehensive association studies are lacking. We hypothesized that variants in nuclear-encoded mitochondrial genes influence susceptibility to SCZ. METHODS: We conducted gene-based and gene-set analyses using summary association results from the Psychiatric Genomics Consortium Schizophrenia Phase 2 (PGC-SCZ2) genome-wide association study comprising 35,476 cases and 46,839 control subjects. We applied the MAGMA method to three sets of nuclear-encoded mitochondrial genes: oxidative phosphorylation genes, other nuclear-encoded mitochondrial genes, and genes involved in nucleus-mitochondria crosstalk. Furthermore, we conducted a replication study using the iPSYCH SCZ sample of 2290 cases and 21,621 control subjects. RESULTS: In the PGC-SCZ2 sample, 1186 mitochondrial genes were analyzed, among which 159 had p values <.05 and 19 remained significant after multiple testing correction. A meta-analysis of 818 genes combining the PGC-SCZ2 and iPSYCH samples resulted in 104 nominally significant and nine significant genes, suggesting a polygenic model for the nuclear-encoded mitochondrial genes. Gene-set analysis, however, did not show significant results. In an in silico protein-protein interaction network analysis, 14 mitochondrial genes interacted directly with 158 SCZ risk genes identified in PGC-SCZ2 (permutation p = .02), and aldosterone signaling in epithelial cells and mitochondrial dysfunction pathways appeared to be overrepresented in this network of mitochondrial and SCZ risk genes. CONCLUSIONS: This study provides evidence that specific aspects of mitochondrial function may play a role in SCZ, but we did not observe its broad involvement even using a large sample. (AU) | |
| FAPESP's process: | 14/01585-5 - De novo and rare inherited variants in obsessive-compulsive disorder |
| Grantee: | Carolina Cappi |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |