Heritability of acoustic startle magnitude and latency from the consortium on the genetics of schizophrenia

Genome-wide Association of Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia (COGS) Study

“…Such endophenotypes are intrinsic to the clinical presentation of schizophrenia, with clear deficits observed in patients with schizophrenia compared with healthy comparison participants (HCPs) and intermediate values observed for unaffected first-degree relatives. [11][12][13][14][15][16] Candidate gene association and linkage analyses of the COGS phase 1 (COGS-1) families implicated a network of genes related to neuregulin and glutamate signaling pathways and synaptic plasticity as underlying endophenotype deficits in schizophrenia, [17][18][19] consistent with the findings of other studies evaluating common, rare, and de novo variation in relation to a schizophrenia diagnosis. 2,20,21 Herein we report the initial findings from the GWAS of these endophenotypes in the independent phase 2 (COGS-2) cohort of patients with schizophrenia and HCPs, which confirm and extend previous results and show consistency with studies of schizophrenia diagnosis in large samples.…”

“…At an enrichment threshold, we found support for the gene network identified through candidate gene association and linkage studies of the COGS-1 families. [17][18][19] In addition to implicating glutamate dysfunction in schizophrenia, many of the genes in this network and those newly identified through GWAS of these endophenotypes form part of the DISC1 (OMIM 605210) regulome for which rare, disruptive variants have been associated with schizophrenia and low cognitive ability in childhood. 32 Such convergence at the pathway level may be more likely to be observed and more meaningful than concordance at the level of an individual gene or SNP in illuminating the underlying neurobiological dysfunction in schizophrenia.…”

107. Genome-Wide Association of Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia (COGS) Study

“…Such endophenotypes are intrinsic to the clinical presentation of schizophrenia, with clear deficits observed in patients with schizophrenia compared with healthy comparison participants (HCPs) and intermediate values observed for unaffected first-degree relatives. [11][12][13][14][15][16] Candidate gene association and linkage analyses of the COGS phase 1 (COGS-1) families implicated a network of genes related to neuregulin and glutamate signaling pathways and synaptic plasticity as underlying endophenotype deficits in schizophrenia, [17][18][19] consistent with the findings of other studies evaluating common, rare, and de novo variation in relation to a schizophrenia diagnosis. 2,20,21 Herein we report the initial findings from the GWAS of these endophenotypes in the independent phase 2 (COGS-2) cohort of patients with schizophrenia and HCPs, which confirm and extend previous results and show consistency with studies of schizophrenia diagnosis in large samples.…”

“…At an enrichment threshold, we found support for the gene network identified through candidate gene association and linkage studies of the COGS-1 families. [17][18][19] In addition to implicating glutamate dysfunction in schizophrenia, many of the genes in this network and those newly identified through GWAS of these endophenotypes form part of the DISC1 (OMIM 605210) regulome for which rare, disruptive variants have been associated with schizophrenia and low cognitive ability in childhood. 32 Such convergence at the pathway level may be more likely to be observed and more meaningful than concordance at the level of an individual gene or SNP in illuminating the underlying neurobiological dysfunction in schizophrenia.…”