A very important and enlightening article; a must read - here:
"This article, and many like it, poses the issue as a general failure of human genomics, but then proceeds to critique only one sub-field: complex disease genetics, the study of multifactorial diseases such as type 2 diabetes and heart disease. Complex disease genetics is in some ways an easy target: in its most modern form the field is only four years old, with its birth dating to the first genome-wide association studies (GWAS) published in mid-2007. In that time the field has uncovered an astonishing number of (independently replicated) genetic variants associated with human disease, but our understanding of the genetics of complex traits is still in its infancy.
Yet Latham and his ilk allow their sniping at complex disease genetics to ricochet off into the broader field of human genomics. Whatever you feel about the success of complex disease genetics, proclaiming “the failure of the genome” does an indisputable disservice to the areas where genetics has made a huge difference both to science and to the lives of patients: for instance, the unravelling of hundreds of severe inherited diseases, and major advances in our understanding of the biology of cancer.
For weakly genetic diseases, such as type 2 diabetes, known genetic factors account for around 2% of the variance of the disease. Compare this to 1% for smoking, and 9% for body-mass index. For more strongly genetic diseases we can do far better. For Crohn’s disease, a form of inflammatory bowel disease, newly discovered variants can explain around 12% of variance, compared to 3% for smoking (the strongest measurable non-genetic predictor of life-time risk). The biggest success story of the new breed of genetic studies is age-related macular degeneration, a common eye disease, for which recently discovered genetic variants can explain around 50% of variance in disease risk.
The genetic variants discovered so far explain only a fraction (albeit a useful fraction) of complex disease risk. However, the usefulness of this research far outweighs the risk it explains; it gives us a database of regions of the human genome that are involved in each disease, containing a range of genes with a variety of functions, each of which we can then investigate biologically. This sort of research has uncovered new mechanisms involved in a range of diseases: for instance, the previously unappreciated importance of a biological process called autophagy in the etiology of Crohn’s disease, and the role of lipid metabolism in Alzheimer’s. The better we understand the mechanism of disease, the more likely we are to be able to identify drug targets for pharmaceutical intervention."
"This article, and many like it, poses the issue as a general failure of human genomics, but then proceeds to critique only one sub-field: complex disease genetics, the study of multifactorial diseases such as type 2 diabetes and heart disease. Complex disease genetics is in some ways an easy target: in its most modern form the field is only four years old, with its birth dating to the first genome-wide association studies (GWAS) published in mid-2007. In that time the field has uncovered an astonishing number of (independently replicated) genetic variants associated with human disease, but our understanding of the genetics of complex traits is still in its infancy.
Yet Latham and his ilk allow their sniping at complex disease genetics to ricochet off into the broader field of human genomics. Whatever you feel about the success of complex disease genetics, proclaiming “the failure of the genome” does an indisputable disservice to the areas where genetics has made a huge difference both to science and to the lives of patients: for instance, the unravelling of hundreds of severe inherited diseases, and major advances in our understanding of the biology of cancer.
For weakly genetic diseases, such as type 2 diabetes, known genetic factors account for around 2% of the variance of the disease. Compare this to 1% for smoking, and 9% for body-mass index. For more strongly genetic diseases we can do far better. For Crohn’s disease, a form of inflammatory bowel disease, newly discovered variants can explain around 12% of variance, compared to 3% for smoking (the strongest measurable non-genetic predictor of life-time risk). The biggest success story of the new breed of genetic studies is age-related macular degeneration, a common eye disease, for which recently discovered genetic variants can explain around 50% of variance in disease risk.
The genetic variants discovered so far explain only a fraction (albeit a useful fraction) of complex disease risk. However, the usefulness of this research far outweighs the risk it explains; it gives us a database of regions of the human genome that are involved in each disease, containing a range of genes with a variety of functions, each of which we can then investigate biologically. This sort of research has uncovered new mechanisms involved in a range of diseases: for instance, the previously unappreciated importance of a biological process called autophagy in the etiology of Crohn’s disease, and the role of lipid metabolism in Alzheimer’s. The better we understand the mechanism of disease, the more likely we are to be able to identify drug targets for pharmaceutical intervention."
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