In the midst of studying Chronic Multifactorial Diseases the distinction between those caused by 1 mutation (monogenic) or multiple ones (polygenic) came up. I was asked by my teacher
to find more examples to fit the following: A polygenic disorder or a disorder that is thought to have an underlying genetic cause (or a range of underlying genetic causes)
Defining terms is important & it can be annoying to have those terms redefined.
So, I answered:
Using the term ‘genetic causes’ when discussing polygenic diseases is problematic for 2 reasons. First, to many researchers and most laymen, it implies that it is only a matter of time before these genes enact diseased phenotypes, as if on a count-down. Second and more importantly, it assumes there is a direct causal path between the emergence of phenotype from genotype. These ‘genetic causes’ are usually derived from GWAS (Genome Wide Association Studies) which make statistical claims based on associations of phenotypes and specific mutations – not biochemical, causal arguments. With these points in mind and in contrast to them, the term ‘genetic predispositions’ is much less problematic. It recognizes statistical associations between genes/mutations and phenotypes, whereby having certain genotypes makes it more or less likely to see a certain phenotype emerge but ignores causal arguments (since it cannot make them).
Type II Diabetes Mellitus (T2D) is a disease of insulin resistance causing glycemic control issues. It is considered a chronic and progressive lifestyle disease by the Australian Diabetes Association and the American Diabetes Association. Its aetiology stems in large part from modern lifestyle factors, chief amongst which nutritional ones. However, it is incorrect to call it a chronic and progressive disease. It is considered as such because most diabetics manage their disease by covering their dietary carbohydrate load with exogenous insulin. In this scenario, it does become chronic and progressive. For in depth discussions of why this is the case with the accompanying references and clinical case reports, please watch video presentations by Dr. Jason Fung. Currently, the best treatment for slowing, halting or reversing T2D involves a nutritional intervention which lowers ones total (and especially refined) dietary carbohydrate load to reduce insulin resistance and thus achieve better glycemic management. Assuming an isocaloric macronutrient shift, this automatically entails increasing the total fat load. A focus on lifestyle interventions is all the more logical considering 36 genes identified as predisposing people to diabetes can explain 10% of why people get it. Additional lifestyle factors relevant to T2D are near innumerable, although chief amongst them are sleep and exercise.
My course still uses saturated fat as an example of lifestyle factors negatively affecting CVD/CAD. It’s a sad state of affairs and testifies to how slow and conservative the medical profession is when it comes to updating guidelines.