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The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets.
Methods
Using a large case–control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status.
Results
Over and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD.
Conclusions
Results indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
The period covered in this volume is one which begins with the emergence of anti-slave trade attitudes in Europe, and ends on the eve of European colonial conquest. But except for white conquests in Algeria and South Africa, and colonies of free Blacks on the west coast, the theme is that of African independence, initiative and adaptation in the last phase of its pre-colonial history. Under greater external pressures than ever before, from European trade, exploration, missionary and political activity, African history in this period moved with greater momentum and larger scale than in past ages, with rapid changes in economic and political life. In general the approach in this volume is through chapters focusing on regions of Africa, each written by an established authority in his field. Concluding chapters survey the activities of Europeans in Africa, and those of Africans and their descendants overseas.
This bibiliography contains a list of reference materials and books related to history of eighteenth century Africa. The primary source-materials for this period of Egyptian history are abundant, but by no means fully or systematically exploited. The accounts of European travellers and residents in Egypt are less important than for an earlier period, but exception must be made of E. W. Lane, The manners and customs of the modern Egyptians first published in London in 1836, many numerous later editions. The abundant periodical literature on the period is listed in J. D. Pearson, Index Islamicus, 1906-1955 and its Supplements. There is a great wealth of source-material for the nineteenth-century history of Ethiopia and the Horn. The political and military history of the Ethiopian state, is dealt within a number of chronicles, in the Ge'ez language and mostly anonymous for the first half of the century, thereafter in Amharic as well as Ge'ez and with named or at least identifiable authors.
This volume is concerned with a period of African history which has traditionally been defined by events emanating from Europe. The year 1790 roughly marks the beginnings of the effective impact of the British anti-slavery movement on West Africa, where the freed slave colony of Sierra Leone was already struggling to establish itself. Protestant missionary enterprise in West and South Africa had begun. In 1795 the British first occupied the Cape of Good Hope, while three years later Napoleon's occupation of Egypt launched the movement of ‘modernization’ in North Africa. In succeeding decades the impact of European traders, missionaries and consuls increasingly began to affect the internal social, political and economic balances within African societies. The choice of 1870 as the terminal date for this volume is obviously dictated by the beginnings of the European scramble for African territory which will be a major theme of volume 6. The period can thus be considered as one dominated by the theme of Africa's growing contact with Europe, as a time of slow penetration and preparation by Europeans for the coming of partition and colonial rule.
Such a perspective, however, offers a somewhat irrelevant pattern for the history of the continent as a whole. Though Bantu in South Africa, or Arabs in Algeria, felt the direct impact of European settler colonization, elsewhere in the continent the vast mass of Africans rarely saw a European, and Europe influenced their lives only indirectly or at second-hand, except for those who lived in coastal areas where there was a direct European presence.
Africa, like Europe, is a continent which has exported millions of colonists, who through their labours and initiative created the ‘New World’ of North and South America, with all that implies for the shape of the modern world. The African emigrants, almost without exception, were taken from Africa by force, and colonized America and the Caribbean as slave labourers. Thus, whilst helping to create the New World by their labour, the historical legacy of African immigration to the American hemisphere has left deep and bitter social, economic and political problems which are still far from solution. The period 1790– 1870 represents a great watershed in this historical movement of world significance. It is not, perhaps, a theme of Africa's domestic history, but none the less one which, through its effects on the relationships of ‘white’ and ‘black’ races and their attitudes to one another, has constantly had the effect of directly influencing the development of African, as well as European and American history.
The essential feature of the period under review is that it witnessed a revolutionary transformation in the legal and civil status of Africans and people of African descent living overseas. In 1770, although there were significant groups of free ‘people of colour’ in North and South America, the Caribbean, and Britain, they were small in number, and emancipated by individual acts, as part of no movement hostile to slavery as such. In general in 1770 white people felt it to be acceptable and normal that the status of black men outside Africa should be that of slavery.