Introduction
Most human genetic traits can be either monogenic or complex. Monogenic traits are characterized by their classical patterns of inheritance within families and are significantly influenced by pathogenic variation within a single gene. While monogenic traits serve as the basis for "classic" genetics, it has become known that conditions in which inheritance fully adheres to Mendelian principles are uncommon. Complex traits result from variations in several genes interacting with behavioral and environmental factors. It does not follow easily predictable patterns of heredity. In this topic, complex traits in genetics are explained.
What Are Complex Traits in Genetics?
Complex traits are affected by multiple factors, including environmental or genetic factors. It is otherwise known as qualitative traits, essential for medicine, agriculture, and evolution. It contrasts simple genetic traits, where changes in a single gene regulate variations. Huntington's disease (a rare genetic disease that results in the gradual degradation of brain nerve cells) and cystic fibrosis (a genetic disorder caused by faulty genes) are two examples of simple traits. Each of these traits is due to a specific gene mutation that affects the function of that gene. Thousands of diseases are caused by a single gene, but these are rare. Mostly, any trait that is not simple is considered complex. If only a few genes affect a trait, it is said to be "oligogenic." When many different genes affect a trait, it is said to be "polygenic." When other non-genetic factors are involved, it is called multifactorial.
Diseases inherited as complex traits are often more common in populations, such as autism, heart disease, Alzheimer's disease, cancer, asthma, and diabetes. Many factors can influence a complex disease. Most commonly, these traits have multiple genes, and differences in these genes can influence disease risk. Hence, complex traits result from gene-gene and gene-environment interactions, genetic variability, and other unknown factors.
What Role Do Genes Play in Complex Disease?
Complex traits are difficult for scientists to research and even harder to understand because numerous factors are involved. It is because various factors do not affect all characteristics. For example, if three genes are involved in a trait, the simplest hypothesis is that each gene accounts for about one-third of the genetic influence on the trait. When the effects of genetic mutations can be added together, this is called an additive effect. It is also necessary to multiply the effects of genetic mutations instead of adding them together, known as a multiplicative effect.
Both additive and multiplicative effects suggest that each gene variant has an effect and increases the overall effect when more genes are involved. But in certain conditions, two or more gene variations may need to be present simultaneously for any effect to be seen.
In simple traits, alterations within the gene result in significant changes in how the gene's product (the protein it codes for) behaves. These mutations are usually considered causative since having them is sufficient to cause the disease. In other words, carrying the mutation is enough to cause the disease. These are referred to as causal genes.
In complex traits, gene changes are usually insufficient to cause the trait. However, these variances may raise or decrease the likelihood of developing the condition. These genes and their variants are commonly referred to as susceptibility genes and susceptibility alleles. A complex disease is caused by a particular combination of susceptibility alleles spread across several genes, possibly involving environmental variables.
What Is an Example of a Complex Trait?
Alzheimer's disease is defined by a gradual decrease in brain function, which typically begins with memory loss. Four genes are known to be involved in the development of this disease. It can be caused by rare mutations in three separate genes (on different chromosomes). A common variant in a fourth gene called ApoE raises the risk of developing this disease nearly threefold if a person has one copy of the allele (named e4) and approximately tenfold if they have two copies.
These four genes account for less than half of all genetic influences in Alzheimer's disease, indicating that additional genes that have not yet been found are equally significant. Environmental risk factors can also have an impact. For instance, while a serious head injury raises the risk of getting Alzheimer's disease, using certain anti-inflammatory drugs like Ibuprofen decreases that risk.
What Effect Does the Environment Have on Complex Disease?
Genes are not the only factors that can influence a complex trait. Environmental factors can also play an important role and vary among traits. Lung cancer is a prominent example of this. It is significantly increased by cigarette smoking. Smoking also appears to impact certain eye problems and other conditions, such as age-related macular degeneration. The presence of specific alleles of susceptibility genes is also a risk factor, but not every chronic smoker will acquire lung cancer or eye disease.
Other risk factors, such as gender, age, occupation, level of education, alcohol consumption, and other lifestyle indicators, can help detect other environmental factors that may be more difficult to identify directly. For example, estrogen's influence is not directly measured but may be detected by identifying a gender effect on the chance of developing the disease. In addition, the degree of environmental effect might vary based on the individual's exposure. For instance, the number of cigarettes smoked daily or the number of years a person has smoked can alter the effects of smoke exposure.
How Do Genes and Environmental Factors Interact?
Genes and environmental factors can work independently or together to generate a complex phenotype. The effects can be epistatic, multiplicative, or additive.
Lung disease is one example of a multiplicative effect. Some people have an alpha-antitrypsin gene variant that significantly increases their lung disease risk. Individuals with this variant who smoke regularly have a higher risk of developing lung disease. Other genes associated with cancer include tumor suppressors, whose specific alleles can affect the chances of developing breast cancer.
Conclusion
Most genetic traits can be categorized as complex or monogenic. Complex trait disorders are ones that cannot be attributed to changes in a single gene. As previously stated, complex traits are determined through interaction with different genetic and environmental factors. Therefore, it is essential to understand complex traits and how genetic and environmental factors interact with the disease to promote health and combat disease.
