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Genetic studies of body mass index yield new insights for obesity biology
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (
P
< 5 × 10
−8
), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.
Genetic correlates of obesity
In the second of two Articles in this issue from the GIANT Consortium, Elizabeth Speliotes and collegues conducted a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), commonly used to define obesity and assess adiposity, to find 97 BMI-associated loci, of which 56 were novel. Many of these loci have significant effects on other metabolic phenotypes. The 97 loci account for about 2.7% of BMI variation, and genome-wide estimates suggest common variation accounts for more than 20% of BMI variation. Pathway analyses implicate the central nervous system in obesity susceptibility including synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Journal Article
Barriers to Democracy
Democracy-building efforts from the early 1990s on have funneled billions of dollars into nongovernmental organizations across the developing world, with the U.S. administration of George W. Bush leading the charge since 2001. But are many such \"civil society\" initiatives fatally flawed? Focusing on the Palestinian West Bank and the Arab world, Barriers to Democracy mounts a powerful challenge to the core tenet of civil society initiatives: namely, that public participation in private associations necessarily yields the sort of civic engagement that, in turn, sustains effective democratic institutions. Such assertions tend to rely on evidence from states that are democratic to begin with. Here, Amaney Jamal investigates the role of civic associations in promoting democratic attitudes and behavioral patterns in contexts that are less than democratic. Jamal argues that, in state-centralized environments, associations can just as easily promote civic qualities vital to authoritarian citizenship--such as support for the regime in power. Thus, any assessment of the influence of associational life on civic life must take into account political contexts, including the relationships among associations, their leaders, and political institutions. Barriers to Democracy both builds on and critiques the multifaceted literature that has emerged since the mid-1990s on associational life and civil society. By critically examining associational life in the West Bank during the height of the Oslo Peace Process (1993-99), and extending her findings to Morocco, Egypt, and Jordan, Jamal provides vital new insights into a timely issue.
eBook
Building Business in Post-Communist Russia, Eastern Europe, and Eurasia
Prior to 1989, the communist countries of Eastern Europe and the USSR lacked genuine employer and industry associations. After the collapse of communism, industry associations mushroomed throughout the region. Duvanova argues that abusive regulatory regimes discourage the formation of business associations and poor regulatory enforcement tends to encourage associational membership growth. Academic research often treats special interest groups as vehicles of protectionism and non-productive collusion. This book challenges this perspective with evidence of market-friendly activities by industry associations and their benign influence on patterns of public governance. Careful analysis of cross-national quantitative data spanning more than 25 countries, and qualitative examination of business associations in Russia, Ukraine, Kazakhstan and Croatia, shows that postcommunist business associations function as substitutes for state and private mechanisms of economic governance. These arguments and empirical findings put the long-standing issues of economic regulations, public goods and collective action in a new theoretical perspective.
eBook
A survey of voluntaristics : research on the growth of the global, interdisciplinary, socio-behavioral science field and emergent inter-discipline
\"This article provies survey of the growth of research on Nonprofit Sector and Voluntary Action Research, now termed simply voluntaristics. The author founded the organized, global interdisciplinary, socio-behavioral science field of voluntaristics in 1971, with his formation and establishment of the Association for Research on Nonprofit Organizations and Voluntary Action (ARNOVA; www.arnova.org). Both ARNOVA, and its interdisciplinary, academic journal, Nonprofit and Voluntary Sector Quarterly (NVSQ), have served as initial models for the global diffusion of this interdisciplinary field, now present in all inhabited continents and with upwards of 20,000 academic participants in at least 130 nations and territories, and likely more.\"
Book
Association analyses based on false discovery rate implicate new loci for coronary artery disease
Hugh Watkins and colleagues meta-analyze data from the UK Biobank along with recent genome-wide association studies for coronary artery disease. They identify 13 new loci that were genome-wide significant and 243 loci at a 5% false discovery rate.
Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (
P
< 5 × 10
−8
) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs.
1
,
2
,
3
,
4
). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT;
n
cases
= 10,801) as well as a stricter definition without angina (HARD;
n
cases
= 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS
2
,
3
. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold
2
, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.
Journal Article