HOW DOES COMPLEX GENETICS AFFECT METABOLIC DISEASES?
Complex metabolic diseases such as diabetes and obesity affect a staggering percentage of the population and a great deal of scientific effort is being devoted to unraveling the complex interplay of genes and environment that cause such diseases. The onset of type 1 diabetes is often in childhood or young adulthood and involves the loss of beta islet cells that produce insulin; genes that have been implicated are involved in immune function (e.g., HLA) and beta cell function. Patients with type 1 diabetes often produce antibodies that target and attack proteins on the beta islet cells, thus contributing to beta cell loss. Type 2 diabetes is caused by progressively increasing dysfunction in the body’s response to the glucose-regulating factor, insulin. Although type 2 diabetes is strongly linked to obesity, there are significant genetic factors at play. Not all obese individuals will develop type 2 diabetes, while many lean individuals will develop the disease, and we currently have a poor understanding of what makes these individuals unique. Obesity itself is highly complex, and although diet and exercise are clearly contributing factors, recent research has implicated genetic factors and even the composition of the microbial population in the gut. A third, less common form of diabetes exists and is referred to as MODY for Maturity Onset of Diabetes in the Young. It is often linked to mutations in one of a small number of genes (~10) that can cause disease by reducing the ability of the pancreas to produce insulin. MODY is monogenic and is not a complex genetic disease.
Large genetic mapping studies spanning thousands of people have been performed for analyzing type 1 and type 2 diabetes, obesity, and other disorders such as elevated cholesterol. These have identified over one hundred genes associated with these various diseases. As with complex neurological disorders, in each case, although many genes have been identified, the genetic contribution of these genes in total is estimated to be 10%–20%, depending upon the disease. Thus, additional genes remain to be discovered. Importantly for each of the diseases, environmental factors and pathogen infections contribute to the disease, as described later in the gene– environment and infectious disease articles. Thus, it is likely that gene–gene and gene–environment interactions contribute to each of these diseases. Overall, because of the myriad of factors that contribute to complex diseases, each person will have his/her own risk for these diseases, based on his/her personal genetic and environmental contributions.