The Genetic Landscape of Renal Complications in Type 1 Diabetes

Diabetes is the leading cause of end stage renal disease. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2,843 subjects, we estimated that the heritability of diabetic kidney disease was 35% ( p=6x10-3 ). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index ( p=2.2×10-5) and the risk of type 2 diabetes (p=6.1x10-4 ) were associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation ( p=1.1×10-4 ). Pathway analysis implicated ascorbate and aldarate metabolism ( p=9×10-6), and pentose and glucuronate interconversions ( p=3×10-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.  

Commentary on Star Chamber Decree 1637

A decree of the Star Chamber designed to regulate the printing of all literary works, whether ecclesiastical or secular in nature. The decree further entrenched the significance and validity of ‘stationers' copyright' in requiring that no work be printed without first being entered on the Company of Stationers' Register Book. The decree also provided that any materials printed thereafter were to carry both the name of the printer and the author of the work.
The commentary describes how, by comparison with earlier decrees (see: uk_1566; uk_1586), the 1637 Decree provided a more elaborate system for licensing both ecclesiastical and secular works as well as a more comprehensive set of regulations to govern the operation of the printing trade. As a regulatory measure, it is widely regarded as representing the high point of the Company of Stationers' control and authority over the book trade.

Commentary on the Licensing Act 1662

Legislation prohibiting the publication of any literary work without prior licence.
Drawing upon both the Star Chamber Decree 1637 (uk_1637) and the Acts Regulating Printing during the Interregnum (see: uk_1643 and associated documents), the Licensing Act set out a comprehensive set of provisions concerning both the licensing of the press and the regulation and management of the book trade. In addition, it confirmed the rights of those holding printing privileges (or patents) granted in accordance with the royal prerogative (see for example: Day's privilege for The Cosmographical Glass (uk_1559b)) as well as those who had registered works with the Stationers' Company (uk_1557). It also introduced the first legal library deposit requirement. In force between 1662 and 1679, and then again between 1685 and 1695, the Act represents the last occasion on which the censorship of the press was formally and strategically linked to the protection of the economic interests of the Stationers' Company. Its lapse led the Stationers' Company to lobby parliament for renewed protection, ultimately resulting in the passing of the Statute of Anne 1710 (uk_1710).