Genetics and Disease: Guyton & McCance Chapters

Genes, Environment, Lifestyle, and Common Diseases

• The presentation discusses how genes, environment, and lifestyle influence common diseases.
• Module 2 focuses on describing gene influence on bodily structure and function, and how defects in genes can lead to recognizable genetic diseases. (Guyton chapter 3, McCance chapters 4, 5, and 6)
• Further study from chapter 5 in McCance is recommended.

Incidence of Disease in Populations

• Incidence rate: the number of new cases of a disease reported during a specific period (typically one year).
• Prevalence rate: the proportion of the population affected by a disease at a specific point in time.
• Prevalence rate of diseases like AIDS is often higher than incidence rates due to the survival periods of those with the disease.
• The prevalence of diseases varies in different populations (e.g., cystic fibrosis is more common in Europeans than Asians, sickle cell disease is more common in African Americans).
• Environmental factors play a role in the incidence of diseases like colon and stomach cancer.

Risk Factors

• Relative risk: the increased rate of a disease among exposed individuals compared to non-exposed individuals.
• Heavy smoking is a significant risk factor for lung cancer (24-fold increased risk of death).
• Risk factors for developing diseases can be genetic or lifestyle-related (age, gender, diet, exercise, family history).
• Genes involved in the metabolism of tobacco smoke components increase the risk of lung cancer for smokers.

Multifactorial Inheritance

• Polygenic traits: traits in which variation is thought to be due to multiple genes.
• Multifactorial trait: trait affected by more than one gene, where environmental factors also influence.
• Examples of multifactorial traits include hypertension, coronary heart disease, type 2 diabetes, and some cancers.
• Threshold of liability: a certain level of genetic susceptibility must be reached before a disease manifests.
• This means some individuals have genes that predispose them to the disease, but the disease only manifests if certain environmental factors are present.

Recurrence Risk and Transmission Patterns

• Risk estimation for multifactorial diseases is complex.
• Recurrence risk is influenced by the severity of the disease in the affected individual, the sex of the affected individual, and the closeness of the relationship between the affected individual and the individual at risk.
• Recurrence risk for single-gene diseases decreases by 50% with each degree of relationship, whereas it decreases more quickly in multifactorial diseases.

Twin Studies

• Twins provide a natural laboratory for studying the interplay of genetic and environmental factors.
• Monozygotic (MZ) twins are genetically identical.
• Dizygotic (DZ) twins are fraternal, genetically different but raised in the same environment.
• MZ twins are more concordant for traits determined by genes while DZ twins have similar concordance rates for traits determined by environmental factors.
• Concordance rate: the percentage of twin pairs who both have a trait.
• Twin studies help identify heritability estimates of specific traits.

Adoption Studies

• Adopted children can help determine the influence of genetics and environment influence on disease.
• The prevalence of developing a disease among adopted children whose biological parents had the disease may indicate a genetic component.
• Adopted children may show a correlation with the genetic risk of their biological parents if raised in different environments.
• Environmental factors can affect disease development irrespective of the biological parent's genetic predispositions.

Twins and Adoption Studies - Take Away

• Common diseases are not solely determined by genetics or environment.
• Genetic and non-genetic factors interact to influence the likelihood of developing a disease.

Genetics of Common Diseases

• Some multifactorial disorders arise at birth, others in adolescents or adulthood.
• Examples of multifactorial disorders include heart disease, cancer, diabetes, etc.
• Risk factors for these disorders include obesity, cigarette smoking, hypertension, elevated cholesterol, and positive family history.

Worldwide Prevalence of Hypertension

• Global prevalence of Hypertension is approximately 25-30%.
• Genetic and environmental factors influence blood pressure regulation.
• The renin-angiotensin system is a complex biological pathway involved in blood pressure regulation.

Cancer

• The second leading cause of death in the United States.
• Tobacco use is a significant risk factor for many types of cancer.
• Breast Cancer is a common type, affecting a large proportion of women.
• Genes like BRCA1 and BRCA2 are associated with increased risk of some types of cancer (breast and ovarian).
• Several types of cancer have strong family correlations.
• Colon and prostate are other prominent types of cancer.

Diabetes

• Type 1 diabetes is an autoimmune disorder (0.3-0.5% risk in general population).
• Type 2 diabetes is associated with insulin resistance and is frequently linked with obesity (90% of cases).
• Genetic and environmental factors interact to affect risk for both type 1 and type 2 diabetes.

Obesity

• Obesity is not a disease but a significant risk factor for many diseases.
• Obesity is commonly linked with lifestyle behaviours and environmental components.
• There is a strong familial correlation linking obesity to environmental factors in parents and offspring.

Alzheimer's Disease

• Characterized by progressive dementia and memory loss.
• Amyloid plaques and neurofibrillary tangles are formed in the brain.
• Risk of Alzheimer's doubles in individuals with an affected first-degree relative.
• Genetic predisposition and environmental factors contribute to Alzheimer's development.

Alcoholism

• Diagnosed in 10% of adult males and 3-5% of adult females.
• Risk increases significantly with affected parents, notably siblings.
• Adoption studies highlight increased risk for offspring of alcoholic parents.
• Genetic (alcohol dehydrogenase genes) and environmental factors play a role in alcoholism risk.

Psychiatric Disorders

• Schizophrenia and bipolar disorder are complex psychological disorders.
• Genetic factors play a significant role in risk for these disorders.
• Affected first-degree relatives can greatly increase risk of schizophrenia.
• Twin studies indicate a clear genetic component, and environments play a role.

Conclusions

• More strongly inherited complex disorders generally have earlier onset.
• Lifestyle modifications (diet, exercise, stress reduction) can significantly reduce risk.
• Genetic lesion identification leads to more effective prevention and treatment.