Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

Collecting Sápmi. Early modern collecting of Sámi material culture

This paper presents the research project Collecting Sápmi. Early modern globalization of Sámi material culture and Sámi cultural heritage today, financed by the Swedish Research Council 2014–18. The aim of the project is to examine early modern collecting of Sámi material culture and early descriptions of Sámi culture, primarily in the seventeenth and eighteenth centuries. We aim to study early modern networks of scholars and collectors interested in Sámi material culture, to investigate how and why the collecting was conducted, and to follow the movement of Sámi objects between collections and collectors around Europe. Furthermore, the project aims to discuss the importance of early modern collecting and the collected objects in today’s society. Here, critical issues are raised concerning colonial histories and relations in Sápmi, motivations and ideologies of collecting over time, as well as the rights to Sámi cultural heritage and its management today and in the future

Copper Worlds : A historical archaeology of Abraham and Jakob Momma-Reenstierna and their industrial enterprise in the Torne River Valley, c. 1650-1680

This article analyses the industrial enterprise of the Dutch-born brothers Abraham and Jakob Momma-Reenstierna and their investments in Sápmi and the upper parts of the Torne River Valley, northern Sweden, during the second half of the seventeenth century. The aim is to explore the driving forces behind the industrial projects of the two brothers in a larger global and colonial context. With inspiration from recent critical studies on the simplifications, and Eurocentrism, in earlier understandings of the birth of modernity, we focus on the modernizing processes taking place in the upper part of the Torne River Valley as a meeting zone between local populations and landscapes and external capital. Metal extraction was booming in the seventeenth-century Sámi areas. Both the Danish-Norwegian and the Swedish Crowns invested heavily in the mining of silver, copper and iron. The scientific focus in archaeology and history has hitherto been very much on the state-governed projects, and limited interest has been directed towards the private enterprises. Moreover, there is also a need to study the roles of the local Finnish and Sámi populations, as well as the global connections, in these colonial industrial projects.A Colonial Arena: Landscape, People and Globalization in Inland Northern Sweden in the Early Modern Perio

Intersecting Worlds: New Sweden’s Transatlantic Entanglements

The New Sweden Colony (1638-1655) is often regarded as an anomaly in the context of 17th century Swedish politics and in the context of other European colonies in America. Equally, the colony's importance in the historical narrative of early modern Sweden and colonial America has been modest. However, more recent research on Scandinavian involvement in the Atlantic economy and early modern politics at home and abroad shows that Sweden was actively involved in producing and advancing a colonial agenda and that the relatively short-lived colonial venture in America had long-term effects and consequences.Taking the point of departure in a critical review of the scholarship on New Sweden, this article examines the common image of the colony and identifies several blind spots and points of convergence between New Sweden and Sweden’s other colonial projects. Informed by postcolonial approaches the article examines colonial rhetoric and logic underlying the interactions between the Swedes and the Native Americans and foregrounds practices of the Swedish community in America. It explores the connections between Sweden and the Swedish community in America throughout the 17th and 18th century and the impact of these connections (and this colonial venture) in Sweden and America. The article also draws attention to the close relations and parallels between the colonial practice in New Sweden and Sápmi. This analysis sheds new light on the colony and its role in Sweden and America in the 17th as well as in the 20th century.