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Scott Isaacs Complete Interview

Scott Isaacs, M.D., F.A.C.P., F.A.C.E. is a board-certified endocrinologist and obesity medicine specialist in Atlanta, Georgia, and a faculty member at Emory University School of Medicine. He is a medical expert for ABC Television Networks and the medical director for the HMR Program for Weight Management at Atlanta Endocrine Associates. Since 1998, Dr. Isaacs has focused his medical practice on obesity medicine and endocrinology. Dr. Isaacs attended Emory College and Emory University School of Medicine, continuing for his residency in Internal Medicine and Fellowship in Endocrinology, Lipids, Diabetes and Metabolism. Dr. Isaacs is a Fellow of the American College of Physicians and the American College of Endocrinology.  Dr. Isaacs is past president of the Georgia Chapter of the American Association of Clinical Endocrinologists and currently serves on the national AACE board of directors and chairs the patient education and awareness committee. Dr. Isaacs is past president of the Atlanta Chapter of the Atlanta Diabetes Association.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #143: The Genetics of Type 2 Diabetes Part 5

In spite of the large number of risk variants identified, it is estimated that they explain less than 15% of the heritability of T2DM. The unexplained heritability is an intensely discussed topic in complex genetics, some claiming it as a failure of GWA studies.There are many possible explanations for the missing heritability, including assumptions made about the genetic architecture of the disease and the definitions of heritability.The estimations of heritability explained assumes that only additive affects determine disease risk and that the risk follows the liability threshold model, that is, the genetic and environmental effects sum up to form a normal distribution of liability and that disease arises in individuals surpassing a certain threshold in the distribution [58]. If these assumptions are not true, the estimate of heritability explained will not be correct. However, there are also many other potential explanations for the missing heritability: yet unmapped common variants, distorted parent-of-origin transmission of risk alleles, rare variants, structural polymorphisms (e.g. copy number variations), gene–gene and/or gene–environment interactions (in which epigenetic effects may be important).

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