Genome-wide association studies (GWASs) have been heralded as a major advance in biomedical discovery, having identified ~2,000 robust associations with complex diseases since 2005. Despite this ...success, they have met considerable scepticism regarding their clinical applicability; this scepticism arises from such aspects as the modest effect sizes of associated variants and their unclear functional consequences. There are, however, promising examples of GWAS findings that will or that may soon be translated into clinical care. These examples include variants identified through GWASs that provide strongly predictive or prognostic information or that have important pharmacological implications; these examples may illustrate promising approaches to wider clinical application.
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Over the past 5 years, genomewide association studies have yielded a wealth of insight into genes and chromosomal loci that contribute to susceptibility to disease. This article, the second in the ...Genomic Medicine series, describes the design of these studies and considers the extent to which the data they provide are useful in predicting the risk of disease.
This article describes the design of genomewide association studies and considers the extent to which the data they provide are useful in predicting the risk of disease.
Genomewide association studies — in which hundreds of thousands of single-nucleotide polymorphisms (SNPs) are tested for association with a disease in hundreds or thousands of persons (Figure 1) — have revolutionized the search for genetic influences on complex traits.
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Such conditions, in contrast with single-gene disorders, are caused by many genetic and environmental factors working together, each having a relatively small effect and few if any being absolutely required for disease to occur. Although complex conditions have been referred to as the geneticist's nightmare,
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in the past 5 years genomewide association studies have identified SNPs implicating hundreds of robustly . . .
The shortage of genomic research data in persons of non-European ancestry is impeding our ability to use genomics in the clinical care of non-European individuals. Improved efforts to utilize data on ...non-European populations will increase the quality of genomic research and the inferences drawn from it for people of all backgrounds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The X chromosome lags behind autosomal chromosomes in genome-wide association study (GWAS) findings. Indeed, the X chromosome is commonly excluded from GWAS analyses despite being assayed on all ...current GWAS microarray platforms. This raises the question: why are so few hits reported on the X chromosome? This commentary aims to examine this question through review of the current X chromosome results in the National Human Genome Research Institute Catalog of Published Genome-Wide Association Studies (NHGRI GWAS Catalog). It will also investigate commonly cited reasons for exclusion of the X chromosome from GWAS and review the tools currently available for X chromosome analysis. It will conclude with recommendations for incorporating X chromosome analyses in future studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genome-wide association (GWA) studies use high-throughput genotyping technologies to assay hundreds of thousands of single-nucleotide polymorphisms (SNPs) and relate them to clinical conditions and ...measurable traits. Since 2005, nearly 100 loci for as many as 40 common diseases and traits have been identified and replicated in GWA studies, many in genes not previously suspected of having a role in the disease under study, and some in genomic regions containing no known genes. GWA studies are an important advance in discovering genetic variants influencing disease but also have important limitations, including their potential for false-positive and false-negative results and for biases related to selection of study participants and genotyping errors. Although these studies are clearly many steps removed from actual clinical use, and specific applications of GWA findings in prevention and treatment are actively being pursued, at present these studies mainly represent a valuable discovery tool for examining genomic function and clarifying pathophysiologic mechanisms. This article describes the design, interpretation, application, and limitations of GWA studies for clinicians and scientists for whom this evolving science may have great relevance.
The authors review lessons learned from several recent public health emergencies and argue that we must conduct research during emergencies to improve our capacity to prevent illness and injury. They ...propose policies to facilitate timely research.
In the past decade, a succession of public health emergencies has challenged preparedness and response capacities of government agencies, hospitals and clinics, public health agencies, and academic researchers, in the United States and abroad. The epidemic of the severe acute respiratory syndrome (SARS), the 9/11 terrorist attacks, and the anthrax mailings stand out as signal examples in the early years of the decade. In addition to natural disasters such as the 2010 earthquake in Haiti and the 2012 Superstorm Sandy, other recent events — including the 2009 influenza A (H1N1) pandemic, the Deepwater Horizon oil spill, and the Fukushima Daiichi . . .
Abstract Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic ...medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of “Genomic Medicine Meetings,” under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so.
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Three new studies identify nearly 20 new loci for serum lipid levels using predominantly a prospective cohort study design which also permits extensive and unbiased characterization of environmental ...exposures. Given the known, strong environmental influences on these traits, investigation of gene-environment interactions should be emphasized in attempts to understand the complete epidemiologic and genetic architecture of these complex trail
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