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Cardiff University

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9 researchers0 verified3 linked papers4,470 indexed citations

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2022 · Nature · 2,848 citations

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. A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

2021 · Nature Genetics · 1,622 citations

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

1972 · Programmed Learning and Educational Technology · 0 citations

An Application of Programmed Instruction to Laboratory Work in a Preliminary Physics Course

The physical sciences have received more than their fair share of attention from researchers in the field of educational technology. The new teaching aids and programmed instruction have been applied to both the theoretical and practical sides of all the major science subjects, but invariably these applications have concentrated on the communication of knowledge in the form of facts or procedures to the exclusion of the more subjective and attitudinal aspects of science training. This paper describes an experimental approach to the teaching of a practical physics course to the preliminary year students of a Ghanaian university. The whole course has been re‐orientated so that the practical work is approached in a somewhat unusual way in which particular emphasis is placed on ideas of accuracy. The student is led to develop an appreciation of the errors which occur in the taking of readings and in the calculation of results from those readings. The development of the course, in which extensive use is made of programmed instruction, is described and some of the problems involved in the programming of subjective material such as this are discussed. The results of pre‐ and post‐testing are presented, and gain scores are related to attitude scores as well as other achievement measures.