scholarly journals Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

Science ◽  
2021 ◽  
Vol 373 (6550) ◽  
pp. eabf8683
Author(s):  
Parsa Akbari ◽  
Ankit Gilani ◽  
Olukayode Sosina ◽  
Jack A. Kosmicki ◽  
Lori Khrimian ◽  
...  
Keyword(s):  
Complex Traits ◽  
Large Scale ◽  
The United States ◽  
Protein Coding ◽  
Knock Out ◽  
The United Kingdom ◽  
Body Adiposity ◽  
Coding Variants ◽  
G Protein Coupled ◽  
Diet Model

Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein–coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ~4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.

scholarly journals Some people just want to watch the world burn: the prevalence, psychology and politics of the ‘Need for Chaos’

2021 ◽  
Vol 376 (1822) ◽  
pp. 20200147 ◽  
Author(s):  
Kevin Arceneaux ◽  
Timothy B. Gravelle ◽  
Mathias Osmundsen ◽  
Michael Bang Petersen ◽  
Jason Reifler ◽  
...  
Keyword(s):  
Large Scale ◽  
Latent Profile Analysis ◽  
Profile Analysis ◽  
The United States ◽  
Psychological Needs ◽  
Anglo Saxon ◽  
Theme Issue ◽  
Political Group ◽  
The United Kingdom ◽  
The World

People form political attitudes to serve psychological needs. Recent research shows that some individuals have a strong desire to incite chaos when they perceive themselves to be marginalized by society. These individuals tend to see chaos as a way to invert the power structure and gain social status in the process. Analysing data drawn from large-scale representative surveys conducted in Australia, Canada, the United Kingdom and the United States, we identify the prevalence of Need for Chaos across Anglo-Saxon societies. Using Latent Profile Analysis, we explore whether different subtypes underlie the uni-dimensional construct and find evidence that some people may be motivated to seek out chaos because they want to rebuild society, while others enjoy destruction for its own sake. We demonstrate that chaos-seekers are not a unified political group but a divergent set of malcontents. Multiple pathways can lead individuals to ‘want to watch the world burn’. This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.

scholarly journals The contribution of common regulatory and protein-coding TYR variants in the genetic architecture of albinism

2021 ◽  
Author(s):  
Vincent Michaud ◽  
Eulalie Lasseaux ◽  
David J Green ◽  
Dave T Gerrard ◽  
Claudio Plaisant ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Large Scale ◽  
Diagnostic Yield ◽  
Genetic Diseases ◽  
Gene Encoding ◽  
Protein Coding ◽  
Autosomal Recessive Disorders ◽  
Functional Variants ◽  
Prevalent Disease ◽  
Coding Variants

Genetic diseases have been historically segregated into rare Mendelian and common complex conditions. Large-scale studies using genome sequencing are eroding this distinction and are gradually unmasking the underlying complexity of human traits. We studied a cohort of 1,313 individuals with albinism aiming to gain insights into the genetic architecture of rare, autosomal recessive disorders. We investigated the contribution of regulatory and protein-coding variants at the common and rare ends of the allele-frequency spectrum. We focused on TYR, the gene encoding tyrosinase, and found that a promoter variant, TYR: c.-301C>T [rs4547091], modulates the penetrance of a prevalent, disease-associated missense change, TYR: c.1205G>A [rs1126809]. We also found that homozygosity for a haplotype formed by three common, functional variants, TYR: c.[-301C;575C>A;1205G>A], confers a high risk of albinism (OR>77) and is associated with reduced vision in UK Biobank participants. Finally, we report how the combined analysis of rare and common variants increases diagnostic yield and informs genetic counselling in families with albinism.

The Politics of Veteran Benefits in the Twentieth Century

2020 ◽  
Author(s):  
Martin Crotty ◽  
Neil J. Diamant ◽  
Mark Edele
Keyword(s):  
Soviet Union ◽  
Large Scale ◽  
Public Support ◽  
Political Influence ◽  
The United States ◽  
Research Field ◽  
Treatment Regimes ◽  
The United Kingdom ◽  
The Soviet Union ◽  
Veteran Benefits

What happened to veterans of the nations involved in the world wars? How did they fare when they returned home and needed benefits? How were they recognized — or not — by their governments and fellow citizens? Where and under what circumstances did they obtain an elevated postwar status? This book examines veterans' struggles for entitlements and benefits in the United States, the United Kingdom, Japan, Taiwan, the Soviet Union, China, Germany, and Australia after both global conflicts. It illuminates how veterans' success or failure in winning benefits were affected by a range of factors that shaped their ability to exert political influence. Some veterans' groups fought politicians for improvements to their postwar lives; this lobbying, the book shows, could set the foundation for beneficial veteran treatment regimes or weaken the political forces proposing unfavorable policies. The book highlights cases of veterans who secured (and in some cases failed to secure) benefits and status after wars both won and lost; within both democratic and authoritarian polities; under liberal, conservative, and even Leninist governments; after wars fought by volunteers or conscripts, at home or abroad, and for legitimate or subsequently discredited causes. Veterans who succeeded did so, for the most part, by forcing their agendas through lobbying, protesting, and mobilizing public support. The book provides a large-scale map for a research field with a future: comparative veteran studies.

The Recreational Use of Cannabis

2018 ◽  
Author(s):  
Leslie Iversen
Keyword(s):  
United States ◽  
United Kingdom ◽  
Large Scale ◽  
The United States ◽  
Cannabis Use ◽  
Us States ◽  
The United Kingdom ◽  
Criminal Offenses ◽  
Official Policy ◽  
Recreational Use

Until relatively recently, the use of cannabis has occurred largely in an underground world of illegality. In most countries, cannabis is considered a dangerous narcotic. Possession of cannabis, cultivation of the cannabis plant, or trafficking are criminal offenses, some of which can carry severe penalties. Although this is the official policy of many countries (including the United States and the United Kingdom), in practice cannabis-related offenses are treated leniently. Despite legal bans, there is a large-scale prevalence of cannabis use. Although legalization has occurred in Europe and some US states, this has not led to large increases in consumption. This chapter discusses the recreational use of cannabis, including prevalence, how it is consumed, and where it comes from. It also provides snapshots of legal cannabis use in the state of Colorado and elsewhere.

scholarly journals Organisational culture and safety: an interdependent relationship

2002 ◽  
Vol 25 (6) ◽  
pp. 181 ◽  
Author(s):  
Geoff Clark
Keyword(s):  
Health Care ◽  
Human Error ◽  
Large Scale ◽  
The United States ◽  
Organisational Culture ◽  
System Failures ◽  
The Public ◽  
The United Kingdom ◽  
The Subject ◽  
Health Care Safety

Since the early 1990s,a body of evidence regarding the lack of quality in health care has emerged in many countries including Australia, the United Kingdom, New Zealand and the United States of America. It has brought the subject of health care safety to the top of the policy agenda and the forefront of the public debate worldwide. Studies show not only that failure of quality occurs, but also that it inflicts harm and wastes resources on a large scale. Experts in risk management, both within and outside the health care industry, emphasize system failures and system-driven errors over direct human error, and accentuate the crucial role that organisational culture plays in ensuring safety. Examination of the interrelationship between culture and safety in organisations demonstrates that organisational relationships influence both culture and safety and that effective two-way communication is pivotal to the success of the development of a corporate 'safety culture'.

Employment in Northern Ireland's Civil Service: Social Barriers and Hyperbole Mean Disabled Need Not Apply

2018 ◽  
Vol 13 ◽  
Author(s):  
Jason Olsen
Keyword(s):  
Northern Ireland ◽  
Large Scale ◽  
Civil Service ◽  
People With Disabilities ◽  
The United States ◽  
Disabled People ◽  
Social Barriers ◽  
Disability Theory ◽  
The United Kingdom ◽  
The Us

The representation of people with disabilities in the Northern Ireland Civil Service (NICS) is approximately 44% less than that seen in the civil services of the United States (US) and Great Britain (GB; i.e., the United Kingdom sans Northern Ireland). Various proactive approaches to employing people with disabilities are cited for the success of the US and GB's efforts to increase the representation of disabled people in their civil services. This is important because governments as employers can be the catalyst for large-scale social change. The US and GB governments have demonstrated an intention to be this catalyst. They have done this by (a) establishing goals for the hiring of disabled people; (b) naming executives responsible for reaching these hiring goals; (c) utilising special hiring authorities; (d) executing guaranteed interview schemes; and (e) applying regulations and laws designed to employ and protect people with disabilities. These activities could be adopted in Northern Ireland (NI) to address the current inequalities in the NICS. However, the question remains whether a government that believes it has achieved disability equality in its civil service, despite comparators that say otherwise, can or will make such a concerted effort. An analysis of over 60 US, GB, and NI government and assembly documents, reports, and laws are examined and compared through the lens of critical disability theory (CDT) to identify the disconnect between the representations and the reality of figures presented about the inclusion of those with disabilities in the NICS.

scholarly journals TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0122271 ◽  
Author(s):  
Dorothée Diogo ◽  
Lisa Bastarache ◽  
Katherine P. Liao ◽  
Robert R. Graham ◽  
Robert S. Fulton ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Complex Traits ◽  
Pleiotropic Effects ◽  
Protein Coding ◽  
Coding Variants

Sociocultural aspects of consanguinity

2015 ◽  
Vol 30 (S2) ◽  
pp. S85-S85
Author(s):  
M. Taleb ◽  
M. Ben Salem ◽  
I. Bouchareb
Keyword(s):  
Rural Areas ◽  
Large Scale ◽  
The United States ◽  
World Population ◽  
Migrant Populations ◽  
Consanguineous Marriages ◽  
The United Kingdom ◽  
Genetic Risks ◽  
Related Individuals ◽  
The Mediterranean

Consanguinity is usually defined as the result of a sexual reproduction between two related individuals. It can also refer to populations sharing at least one common ancestor, as those who live within isolates or within communities practicing endogamy. Second or higher order related couples and their offspring represent more than 10% of the current world population. The highest levels of consanguinity are found in the Southern and Eastern shores of the Mediterranean Basin, and the most concerned region extends from the southern shore of the Mediterranean Sea to Southeast Asia through Middle-East, Gulf and India. In Maghreb countries, consanguineous marriages are wide-spread. The rates for this practice vary from 23% in Morocco to 60% in Tunisia, with highest rates being found in rural areas. In Algeria, consanguineous marriages represent more than 38% of all marriages. Large scale migrations from South countries to North countries in the second half of the twentieth century had legal impact on migrants for these specific unions. As a consequence, controversies have been rising in the United States and the United Kingdom especially when a fast decrease of inter-related individuals unions seems unlikely. Consanguinity certainly increases the risk of autosomal recessive pathology, but what about mental pathologies with complex and polygenic heredity? The necessity of an awareness of the genetic risks of consanguinity is as essential in countries where inter-cousin unions are culturally encouraged as among migrant populations in Europe.

scholarly journals Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
James Zou ◽  
Gregory Valiant ◽  
Paul Valiant ◽  
Konrad Karczewski ◽  
Siu On Chan ◽  
...  
Keyword(s):  
Large Scale ◽  
Human Populations ◽  
Protein Coding ◽  
Coding Variants

scholarly journals Quantifying the unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects

2015 ◽  
Author(s):  
James Zou ◽  
Gregory Valiant ◽  
Paul Valiant ◽  
Konrad Karczewski ◽  
Siu On Chan ◽  
...  
Keyword(s):  
Frequency Distribution ◽  
Statistical Power ◽  
Large Scale ◽  
Rare Variants ◽  
Human Populations ◽  
Loss Of Function ◽  
Protein Coding ◽  
Missense Variants ◽  
Healthy Humans ◽  
Coding Variants

As new proposals aim to sequence ever larger collection of humans, it is critical to have a quantitative framework to evaluate the statistical power of these projects. We developed a new algorithm, UnseenEst, and applied it to the exomes of 60,706 individuals to estimate the frequency distribution of all protein-coding variants, including rare variants that have not been observed yet in the current cohorts. Our results quantified the number of new variants that we expect to identify as sequencing cohorts reach hundreds of thousands of individuals. With 500K individuals, we find that we expect to capture 7.5% of all possible loss-of-function variants and 12% of all possible missense variants. We also estimate that 2,900 genes have loss-of-function frequency of less than 0.00001 in healthy humans, consistent with very strong intolerance to gene inactivation.

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