There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.

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Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

The metabolic syndrome

469 Abstract Aims To establish a unified working diagnostic tool for the metabolic syndrome (MetS) that is convenient to use in clinical practice and that can be used world- wide so that data from different countries can be compared. An additional aim was to highlight areas where more research into the MetS is needed. Participants The International Diabetes Federation (IDF) convened a workshop held 12-14 May 2004 in London, UK. The 21 participants included experts in the fields of diabetes, public health, epidemiology, lipidology, genetics, metabolism, nutrition and cardiology. There were participants from each of the five con- tinents as well as from the World Health Organization (WHO) and the National Cholesterol Education Program—Third Adult Treatment Panel (ATP III). The workshop was sponsored by an educational grant from AstraZeneca Pharmaceuticals. Consensus process The consensus statement emerged following detailed discussions at the IDF workshop. After the workshop, a writing group produced a consensus statement which was reviewed and approved by all participants. Conclusions The IDF has produced a new set of criteria for use both epidemio- logically and in clinical practice world-wide with the aim of identifying people with the MetS to clarify the nature of the syndrome and to focus therapeutic strategies to reduce the long-term risk of cardiovascular disease. Guidance is included on how to compensate for differences in waist circumference and in regional adipose tissue distribution between different populations. The IDF has also produced recommendations for additional criteria that should be included when studying the MetS for research purposes. Finally, the IDF has identified areas where more studies are currently needed; these include research into the aetiology of the syndrome. Diabet. Med. 23, 469-480 (2006)

/pdf/metabolic-syndrome-a-new-world-wide-definition-a-consensus-5amrc46uob.pdf

Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation.

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

Abdominal obesity and metabolic syndrome

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60679-X.pdf

National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants

Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. The epidemic is chiefly of type 2 diabetes and also the associated conditions known as 'diabesity' and 'metabolic syndrome'. In conjunction with genetic susceptibility, particularly in certain ethnic groups, type 2 diabetes is brought on by environmental and behavioural factors such as a sedentary lifestyle, overly rich nutrition and obesity. The prevention of diabetes and control of its micro- and macrovascular complications will require an integrated, international approach if we are to see significant reduction in the huge premature morbidity and mortality it causes.

K. G. M. M. Alberti

Papers

Global and societal implications of the diabetes epidemic