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

Parasitic plants indirectly regulate below-ground properties in grassland ecosystems

Parasitic plants are one of the most ubiquitous groups of generalist parasites in both natural and managed ecosystems, with over 3,000 known species worldwide1, 2, 3. Although much is known about how parasitic plants influence host peformance1, 2, 3, 4, their role as drivers of community- and ecosystem-level properties remains largely unexplored5. Parasitic plants have the potential to influence directly the productivity and structure of plant communities because they cause harm to particular host plants, indirectly increasing the competitive status of non-host species6, 7, 8, 9, 10. Such parasite-driven above-ground effects might also have important indirect consequences through altering the quantity and quality of resources that enter soil, thereby affecting the activity of decomposer organisms3, 11, 12, 13. Here we show in model grassland communities that the parasitic plant Rhinanthus minor, which occurs widely throughout Europe and North America14, has strong direct effects on above-ground community properties, increasing plant diversity and reducing productivity. We also show that these direct effects of R. minor on the plant community have marked indirect effects on below-ground properties, ultimately increasing rates of nitrogen cycling. Our study provides evidence that parasitic plants act as a major driver of both above-ground and below-ground properties of grassland ecosystems

Appendix C. A description of the habitats from which leaves and litter were collected for the litter bed experiment, including the names of dominant species, and the hemiparasites most commonly associated with that vegetation type.

A description of the habitats from which leaves and litter were collected for the litter bed experiment, including the names of dominant species, and the hemiparasites most commonly associated with that vegetation type

Appendix D. A table showing distribution of species across habitats and life-form groups.

A table showing distribution of species across habitats and life-form groups

Appendix A. Climate data for the growing seasons (June, July, and August) of 1998 and 1999, and for the whole incubation period (October–September) for litter buried in 1998 and 1999.

Climate data for the growing seasons (June, July, and August) of 1998 and 1999, and for the whole incubation period (October–September) for litter buried in 1998 and 1999