Complex Genetic Disorders The expression of many common diseases such as cardiovascular disease, hypertension, diabetes, asthma, psychiatric disorders, and certain cancers is determined by a combination of genetic background, environmental factors, and lifestyle. A trait is called polygenic if multiple genes contribute to the phenotype or multifactorial if multiple genes are assumed to interact with environmental factors. Genetic models for these complex traits need to account for genetic heterogeneity and interactions with other genes and the environment. Complex genetic traits may be influenced by modifying genes that are not linked to the main gene involved in the pathogenesis of the. | Chapter 062. Principles of Human Genetics Part 25 Complex Genetic Disorders The expression of many common diseases such as cardiovascular disease hypertension diabetes asthma psychiatric disorders and certain cancers is determined by a combination of genetic background environmental factors and lifestyle. A trait is called polygenic if multiple genes contribute to the phenotype or multifactorial if multiple genes are assumed to interact with environmental factors. Genetic models for these complex traits need to account for genetic heterogeneity and interactions with other genes and the environment. Complex genetic traits may be influenced by modifying genes that are not linked to the main gene involved in the pathogenesis of the trait. This type of gene-gene interaction or epistasis plays an important role in polygenic traits that require the simultaneous presence of variations in multiple genes to result in a pathologic phenotype. Type 2 diabetes mellitus provides a paradigm for considering a multifactorial disorder as genetic nutritional and lifestyle factors are intimately interrelated in disease pathogenesis Table 62-7 Chap. 338 . The identification of genetic variations and environmental factors that either predispose to or protect against disease is essential for predicting disease risk designing preventive strategies and developing novel therapeutic approaches. The study of rare monogenic diseases may provide insight into some of genetic and molecular mechanisms important in the pathogenesis of complex diseases. For example the identification of the hepatocyte nuclear factor a HNFa in maturity-onset of diabetes type 4 defined it as a candidate gene in the pathogenesis of diabetes mellitus type 2 Tables 62-2 and 62-8 . Genome scans have identified various loci that may be associated with susceptibility to development of diabetes mellitus in certain populations. Efforts to identify susceptibility genes require very large sample sizes and positive results may .
