Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

Patronage, district creation, and reform in Uganda

The effects of economic and political reforms on patronage in Africa remains unclear. In particular, there is much disagreement about whether structural adjustment programs and democratization have helped to make patronage less pervasive in African politics. Here, I examine the case study of Uganda, which has received much praise for its large-scale economic and political reforms since the late 1980s. However, at the same time, Uganda has also experienced a near-explosion in the number of districts (the highest level of local government), going from 39 to 80 in less than a decade. I examine a variety of potential reasons why these districts might have been created and argue, through the use of both qualitative and quantitative analysis, that district creation has functioned as a source of patronage. Specifically, I show that President Museveni_s government has created new districts as a means to compensate for other patronage resources lost through reforms and that new districts have helped him to continue to win elections. This paper thus constitutes the first rigorous demonstration that the creation of new sub-national political units can constitute a form of patronage and suggests that similar processes may be currently taking place across Afric