Ch5 Genes, Environment, and Multifactorial Diseases in Human Health

What are the main causes of congenital diseases?

Most congenital diseases are not caused by a single gene or chromosome defect, but rather by a combination of genetic components and environmental factors.

What is the difference between incidence rate and prevalence rate?

Incidence rate is the number of new cases of a disease reported during a specific period divided by the population at risk, while prevalence rate is the total number of people affected by a disease (old + new) at a specific point in time divided by the total population.

How is relative risk defined in the context of disease?

Relative risk is the increased rate of a disease among individuals exposed to a risk factor divided by the incidence rate of the disease among individuals not exposed to that risk factor.

What factors can influence the risk of developing a disease?

Factors include age, gender, diet, exercise, and family history of the disease.

What are polygenic traits?

Polygenic traits are variations in traits caused by the effects of multiple genes.

What are multifactorial traits?

Multifactorial traits are variations in traits caused by environmental factors.

What is the purpose of recurrence risks in genetics?

Recurrence risks estimate the probability that a condition present in one or more family members will recur in another relative in the same or future generations.

What factors can affect recurrence risks in multifactorial diseases?

Recurrence risks can be influenced by the number of affected family members, the severity of the disease in the proband, and the sex of the proband.

What is the significance of twin studies in genetics?

Twin studies help determine the relative influence of genetic and environmental factors by comparing traits in monozygotic (identical) and dizygotic (fraternal) twins.

What are concordant and discordant traits in twin studies?

Concordant traits are those shared by both members of a twin pair, while discordant traits are those not shared.

What is the focus of adoption studies in genetics?

Adoption studies focus on children born to parents with a disease who are adopted by parents without the disease to assess disease recurrence.

What is gene-environment interaction?

Gene-environment interaction occurs when a genetic predisposition interacts with an environmental factor, significantly increasing the risk for a disease.

What are congenital diseases?

Congenital diseases are conditions that are present at birth.

What are some examples of congenital malformations?

Examples include phocomelia caused by thalidomide, malformations due to retinoic acid, and those caused by maternal rubella.

How do environmental factors contribute to congenital malformations?

Environmental factors can cause variations in traits that lead to congenital malformations.

What challenges exist in determining recurrence risks for multifactorial diseases?

Challenges include the unknown number of genes contributing to the disease, the precise allelic constitution of parents, and varying environmental effects.

How does the severity of disease in the proband affect recurrence risk?

If the expression of the disease in the proband is more severe, the recurrence risk is higher.

What happens to recurrence risk as the relationship between relatives becomes more distant?

Recurrence risk usually decreases rapidly in remotely related relatives.

What is the role of lifestyle factors in disease risk?

Lifestyle factors, along with genetic predispositions, can significantly influence the risk of developing diseases.

What is the importance of understanding the interaction between genes and environment?

Understanding this interaction helps in assessing the risk and prevention strategies for multifactorial diseases.

What is the significance of studying both MZ and DZ twins?

Studying both types of twins allows researchers to differentiate the effects of genetics from those of the environment.

What is a common outcome of gene-environment interactions?

A genetic predisposition may lead to a much higher risk for a disease when combined with certain environmental factors.

How do twin studies contribute to our understanding of genetic diseases?

They provide insights into the heritability of traits and the influence of environmental factors.

What are multifactorial disorders?

Conditions caused by many contributing factors, also known as complex disorders.

List some examples of multifactorial disorders.

Alcoholism, Alzheimer's disease, arthritis, asthma, cancer, cardiovascular disease, depression, diabetes, epilepsy, multiple sclerosis, Parkinson's disease, obesity, schizophrenia.

What is the potential consequence of atherosclerosis in coronary heart disease?

It can lead to myocardial infarction or stroke.

What factors increase the risk of coronary heart disease?

More affected relatives, affected female relatives, younger age of onset (under 55), autosomal dominant familial hypercholesterolemia, high-fat diet, lack of exercise, smoking, and obesity.

What is hypertension and what are its risks?

Hypertension is a risk factor for heart disease, stroke, and kidney disease.

What percentage of blood pressure variations are genetic?

Between 20% and 40%.

What are some important environmental factors affecting hypertension?

Sodium intake, lack of exercise, stress, and obesity.

What is the second leading cause of death in the United States?

Cancer.

How does tobacco use relate to cancer?

It accounts for one-third of all cancers.

What is the risk of breast cancer for women with a first-degree relative who has the disease?

The risk doubles.

What genetic mutations are linked to an autosomal dominant form of breast cancer?

Mutations in BRCA1 (chromosome 17) and BRCA2 (chromosome 13).

What is the lifetime risk of developing breast cancer with BRCA mutations?

50% to 80%.

What is colorectal cancer's rank in terms of annual deaths in the U.S.?

It is second only to lung cancer.

How much higher is the risk of colorectal cancer for individuals with one affected first-degree relative?

Two to three times higher than the general population.

What genetic mutations are associated with familial adenomatous polyposis?

Inherited adenomatous polyposis coli (APC) gene mutations.

What is the second most commonly diagnosed cancer in men?

Prostate cancer.

What is a significant risk factor for prostate cancer?

A high-fat diet.

What methods are used to detect prostate cancer?

Digital examination and prostate-specific antigen (PSA) test.

What is the leading cause of blindness, heart disease, and kidney failure?

Diabetes mellitus.

What are the two major types of diabetes mellitus?

Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent).

What causes Type 1 diabetes?

Autoimmune destruction of insulin-producing beta cells in the pancreas.

What is the risk for siblings of individuals with Type 1 diabetes?

They face a substantial elevation in risk.

What is the incidence of Type 1 diabetes in offspring of diabetic fathers?

It is higher compared to the general population.

What is the lifelong requirement for individuals with type 1 diabetes?

Insulin

What is the risk of type 1 diabetes in siblings of affected individuals?

Substantial elevation in risk

How does the incidence of type 1 diabetes differ between offspring of diabetic fathers and mothers?

Higher incidence in offspring of diabetic fathers

What is the increased risk percentage for identical (MZ) twins compared to fraternal (DZ) twins for type 1 diabetes?

MZ twins have a 30% to 50% risk, while DZ twins have a 5% to 10% risk

What specific genetic association is linked to type 1 diabetes?

Association of specific human leukocyte antigen (HLA) class II alleles is 40%.

What genetic variation is associated with a 10% increased risk of type 1 diabetes?

Variation in the insulin gene

What percentage of all diabetes cases does type 2 diabetes account for?

More than 90%

What are the primary characteristics of type 2 diabetes?

Insulin resistance or diminished insulin production, with no HMC associations or autoantibodies present.

What does it mean that recurrence risk becomes higher if more than one family member is affected?

Multiple affected relatives suggest stronger genetic/environmental contribution → recurrence risk

What are the risk factors for developing type 2 diabetes?

Obesity and a positive family history; exercise has a preventive effect.

What is the recurrence risk for MZ twins and first-degree relatives for type 2 diabetes?

MZ twins have a 90% risk; first-degree relatives have a 15% to 40% risk.

Which gene variant is associated with a 50% increased risk of type 2 diabetes?

Variant of TCF7L2

What is the BMI threshold for obesity?

A BMI greater than 30.

What health risks are associated with obesity?

Heart disease, stroke, cancer (prostate, breast, colon), and type 2 diabetes.

What is the heritability estimate range for body weight based on twin studies?

Between 0.60 and 0.80.

What are the genetic factors related to obesity?

Genes for leptin and its receptors.

What are the main characteristics of Alzheimer disease (AD)?

Progressive dementia, loss of memory, amyloid plaques, and neurofibrillary tangles.

How does having a first-degree relative with AD affect risk?

It doubles the risk of developing AD.

What mutations are associated with early-onset Alzheimer disease?

Mutations in presenilin 1 (PS1), presenilin 2 (PS2), and amyloid-beta precursor protein (APP) gene.

What is the increased risk of alcoholism for individuals with an alcoholic parent?

Three to five times higher.

What do adoption studies reveal about the risk of alcoholism?

Offspring of an alcoholic parent have a fourfold increased risk, even when raised by nonalcoholic parents.

What is the risk of schizophrenia for offspring of affected parents?

10 times higher if one parent is affected; approximately 20% if both a sibling and a parent are affected; 50% if both parents are affected.

What is the risk percentage for MZ and DZ twins regarding schizophrenia?

MZ twins have a risk of 47%, while DZ twins have a risk of 12%.

What is the genetic contribution to bipolar affective disorder?

60% of the risk is due to genetic factors.

What is the risk increase for bipolar disorder if an individual has an affected first-degree relative?

Between 5% and 10%, compared to a normal risk of 0.5%.

If the expression of the disease in the proband is more severe, how does that affect recurrence risk?

Recurrence risk ↑ (because it's harder for that sex to be affected → stronger predisposition in the family).

How does recurrence risk change in more distant relatives?

Risk decreases rapidly in remotely related relatives.