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Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study
- Source :
- Schizophrenia research, vol 170, iss 1, SCHIZOPHRENIA RESEARCH, vol 170, iss 1, Greenwood, TA; Lazzeroni, LC; Calkins, ME; Freedman, R; Green, MF; Gur, RE; et al.(2016). Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study. SCHIZOPHRENIA RESEARCH, 170(1), 30-40. doi: 10.1016/j.schres.2015.11.008. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/0kk726kp
- Publication Year :
- 2016
- Publisher :
- eScholarship, University of California, 2016.
-
Abstract
- The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes. Genotyping via a custom array of 1536 SNPs from 94 candidate genes identified associations for CTNNA2, ERBB4, GRID1, GRID2, GRIK3, GRIK4, GRIN2B, NOS1AP, NRG1, and RELN across multiple endophenotypes. An experiment-wide p value of 0.003 suggested that the associations across all SNPs and endophenotypes collectively exceeded chance. Linkage analyses performed using a genome-wide SNP array further identified significant or suggestive linkage for six of the candidate endophenotypes, with several genes of interest located beneath the linkage peaks (e.g., CSMD1, DISC1, DLGAP2, GRIK2, GRIN3A, and SLC6A3). While the partial convergence of the association and linkage likely reflects differences in density of gene coverage provided by the distinct genotyping platforms, it is also likely an indication of the differential contribution of rare and common variants for some genes and methodological differences in detection ability. Still, many of the genes implicated by COGS through endophenotypes have been identified by independent studies of common, rare, and de novo variation in schizophrenia, all converging on a functional genetic network related to glutamatergic neurotransmission that warrants further investigation.
- Subjects :
- 0301 basic medicine
Candidate gene
Endophenotypes
Single-nucleotide polymorphism
Medical and Health Sciences
Article
Association
Heritability
03 medical and health sciences
DISC1
0302 clinical medicine
Clinical Research
Genetics
Humans
2.1 Biological and endogenous factors
Genetic Predisposition to Disease
Family
Aetiology
Genotyping
Biological Psychiatry
Psychiatric genetics
Psychiatry
biology
Linkage
Prevention
Human Genome
Psychology and Cognitive Sciences
Genetic architecture
Brain Disorders
Psychiatry and Mental health
Reelin Protein
Endophenotype
030104 developmental biology
Mental Health
biology.protein
Schizophrenia
030217 neurology & neurosurgery
SNP array
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Schizophrenia research, vol 170, iss 1, SCHIZOPHRENIA RESEARCH, vol 170, iss 1, Greenwood, TA; Lazzeroni, LC; Calkins, ME; Freedman, R; Green, MF; Gur, RE; et al.(2016). Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study. SCHIZOPHRENIA RESEARCH, 170(1), 30-40. doi: 10.1016/j.schres.2015.11.008. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/0kk726kp
- Accession number :
- edsair.doi.dedup.....69f96b716e3c32c62cdc4331fef91ebf