Stain, Stanley

https://dh.howard.edu/prom_corres/1136/thumbnail.jp

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Early tracking would improve the operative experience of general surgery residents

Objective(S): High surgical complexity and individual career goals has led most general surgery (GS) residents to pursue fellowship training, resulting in a shortage of surgeons who practice broad-based general surgery. We hypothesize that early tracking of residents would improve operative experience of residents planning to be general surgeons, and could foster greater interest and confidence in this career path. Methods: Surgical Operative Log data from GS and fellowship bound residents (FB) applying for the 2008 American Board of Surgery Qualifying Examination (QE) were used to construct a hypothetical training model with 6 months of early specialization (ESP) for FB residents in 4 specialties (cardiac, vascular, colorectal, pediatric); and presumed these cases would be available to GS residents within the same program. Results: A total of 142 training programs had both FB residents (n = 237) and GS residents (n = 402), and represented 70% of all 2008 QE applicants. The mean numbers of operations by FB and GS residents were 1131 and 1091, respectively. There were a mean of 252 cases by FB residents in the chief year, theoretically making 126 cases available for each GS resident. In 9 defined categories, the hypothetical model would result in an increase in the 5-year operative experience of GS residents (mastectomy 6.5%; colectomy 22.8%; gastrectomy 23.4%; antireflux procedures 23.4%; pancreatic resection 37.4%; liver resection 29.3%; endocrine procedures 19.6%; trauma operations 13.3%; GI endoscopy 6.5%). Conclusions: The ESP model improves operative experience of GS residents, particularly for complex gastrointestinal procedures. The expansion of subspecialty ESP should be considered. © 2010 by Lippincott Williams & Wilkins