National University of Singapore

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.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Biology of GDNF and its receptors — Relevance for disorders of the central nervous system

THE BREEDING BIOLOGY OF THE BLACK‐FACED DIOCH <i>QUELEA QUELEA</i> IN NIGERIA

SUMMARY A study of the breeding biology of Quelea quelea in Nigeria, and particularly at a large breeding colony near Lake Chad, showed that losses of eggs and young were extremely small. 95% of eggs laid hatched successfully, and 87% give rise to fledglings. Nestling deaths were density‐dependent and apparently due to starvation. The incubation period was 10 days or less. By day, eggs were heated to 34°‐ 37° C. by the sun; at night the females incubated. The nestlings were initially fed mainly on insects, their diet gradually changing to one of seeds—mostly of the grass Echinochloa pyramidalis . The deep body temperatures of young birds were determined. It is suggested that the nestlings left the nest after, on average, 11 1 / 2 days to escape intolerable temperature conditions in the nest. Fat reserves were accumulated by nestlings and fledglings, and were utilized when the young became independent. The adults put on fat during the incubation period and lost it during the time spent feeding nestlings. It is concluded that the most common clutch‐size of Q. quelea , which is everywhere three, corresponds to the largest number of young the parents can normally nourish. This conforms to Lack's theory on the significance of clutch‐size, and gives no support to Skutch's opinion that the theory does not apply to tropical birds.