Posts Tagged ‘schizophrenia’

New GWAS SCZ loci (nature genetics 2018)

March 5, 2018

Common #schizophrenia alleles are enriched in mutation-intolerant genes & in regions under strong background selection 50 novel SCZ loci & 145 loci in total, from #GWAS – associated w/ 33 candidate causal genes

We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci.

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
Nature Genetics (2018)

Runs in the Family – The New Yorker

April 11, 2016

Runs in the Family Overview of recent results that #SCZ is due to synaptic overpruning from excessive C4 activity

A magnificently simple theory began to convulse out of the results. Perhaps C4A, like the other immunological factors that Stevens had identified in synapse pruning, marks neuronal synapses destined to be eliminated during normal brain development. During the maturation of the brain, microglia recognize these factors as tags and engulf the tagged synapses. Variations in the C4A gene cause different amounts of the C4A protein to be expressed in the human brain. The overabundance of C4A protein in some people contributes to an excessively exuberant pruning of synapses—thereby decreasing the number of synapses in the brain, which would explain the well-established fact that
schizophrenic patients tended to have fewer neuronal connections. That the symptoms of schizophrenia break loose during the second and third decades of life makes sense, in retrospect: adolescence and early adulthood are periods when synaptic pruning reaches a climax in the regions of the brain that govern planning and thinking.