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Schizophrenia affects nearly 1% of the population ( 1) and has sufficiently high heritability (80%) ( 2) to suggest that identifying genetic risk factors would provide insights into disease mechanisms. These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts. Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48 95% CI, 1.52 to 19.74 P = 0.02) and 1.6% of controls (odds ratio, 5.82 95% CI, 3.00 to 11.28 P = 2.6 × 10 −8). A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18 95% CI, 1.33 to 3.60 P = 1.6 × 10 −3) and 25.4% of controls (odds ratio, 2.74 95% CI, 1.85 to 4.06 P = 2.9 × 10 −7).

Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91 95% CI, 1.39 to 2.63 P = 7.8 × 10 −5) and damaging missense variants in intolerant genes (odds ratio, 2.90 95% CI, 2.02 to 4.15 P = 3.2 × 10 −9). We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes.

We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. Target groups are the global research community and students of today and tomorrow banks, institutional investors and venture capitalists, insurance companies and other financial operators and public decision-makers and legislators.Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia.

The results will support both private and public decision-making while also providing a basis for reforms and regulation of the financial sector. The aim of the programme is to generate benefits by developing good ideas about how financial markets and operators can contribute to more sustainable development of society. Mistra Center for Sustainable Markets (Misum) coordinates the programme in close collaboration with Swedish House of Finance (SHOF). The programme is being run from the Stockholm School of Economics (SSE), based at two leading research institutes there. Practical tools: development of practical tools for financial operators wishing to contribute to sustainable development. Governance: how sustainable is the current financial sector? What can improve the quality of households’ financial services, financial stability and financing of new businesses? Market drivers: how can the financial sector help to establish green innovations and ecofriendly technology? What part can FinTech (new technology for financial services) play here? Policy: what regulations and institutional systems can facilitate a transition to a more sustainable financial system? Green macro: what are the connections between financial markets and the environmental impact of the economy? The various subprojects are divided into five research areas: The projects belong to a range of disciplines: finance, business administration, economics, natural sciences, political science and philosophy. Mistra Financial Systems comprises some 30 research and development projects, hosted at higher education institutions (HEIs) in and outside Sweden. How well are these functions performed at present? What could be done differently? What can be learnt from current experiments and innovation? All these issues are touched on in the research projects included in the programme. banks, pension funds, insurance companies and other institutions, and also financial markets affect a range of critical sustainability issues, such as the environmental impact of the economy and financial stability, but also households’ access to appropriate and efficient financial services. The Mistra Financial Systems research programme investigates how financial markets and operators can contribute to society’s sustainable development.