Transcript Chapter 5 notes

Genes, EnvironmentLifestyle, and Common
Diseases
Chapter 5
Disease in Populations

Incidence rate


Number of new cases of a disease reported during
a specific period (typically 1 year) divided by the
number of individuals in the population
Prevalence rate

Proportion of the population affected by a disease
at a specific point in time
Risk Factors

Relative risk

Incidence rate of a disease among individuals
exposed to a risk factor divided by the incidence
rate of a disease among individuals not exposed
to a risk factor
Multifactorial Inheritance

Polygenic


Multifactorial trait


Variation in traits caused by the effects of
multiple genes
Variation in traits caused by genetic and
environmental or lifestyle factors
Quantitative traits

Traits that are measured on a continuous numeric
scale
Multifactorial Inheritance

Threshold model


Liability distribution
Threshold of liability
Multifactorial Inheritance
Recurrence Risks

Recurrence risks of multifactorial diseases
can change substantially because gene
frequencies as well as environment and
lifestyle factors can differ among populations
Recurrence Risks




Recurrence risk becomes higher if more than one
family member is affected
If the expression of the disease in the proband is
more severe, the recurrence risk is higher
The recurrence risk is higher if the proband is of the
less commonly affected sex
The recurrence risk for the disease usually decreases
rapidly in more remotely related relatives
Nature and Nurture

Nature


Genetics
Nurture

Environmental-lifestyle
Nature and Nurture

Twin studies



Monozygotic (identical)
Dizygotic (fraternal)
Concordant trait


Both members of a twin pair share a trait
Discordant trait

A twin pair does not share a trait
Nature and Nurture

Adoption studies

Children born to parents who have a disease but
are then subsequently adopted by parents lacking
the disease are studied for the recurrence of the
disease
Genetics of Common Diseases

Congenital malformations


Congenital diseases are present at birth or shortly
after birth
Most congenital diseases are multifactorial
Adult Multifactorial Diseases

Coronary heart disease


Potential MI caused by atherosclerosis
Risk increases if:




There are more affected relatives
Affected relatives are female rather than male
Age of onset is younger than 55 years
Autosomal dominant familial
hypercholesterolemia, high-fat diet, lack of
exercise, smoking, and obesity
Familial Hypercholesterolemia




Autosomal dominant
1 in 500 is heterozygous for the FH gene; 1
in 1 million is homozygous for the trait
Serum cholesterol 300 to 400 mg/dL in
heterozygote; 600 to 1200 mg/dL in
homozygote
Cholesterol deposits in arteries and skin
(xanthomas)
Familial Hypercholesterolemia
Hypertension



Risk factor for heart disease, stroke, and
kidney disease
Studies show that 20% to 40% of blood
pressure variations are genetic. This means
that 60% to 80% are environmental.
Causes of hypertension

Sodium intake, lack of exercise, stress, obesity,
smoking, and high-fat intake
Breast Cancer





Affects 12% of American women who live to be 85
If a woman has a first-degree relative with breast
cancer, her risk doubles
Recurrence risk increases if the age of onset in the
affected relative is early and if the cancer is bilateral
An autosomal dominant form of breast cancer (5%
of breast cancers) has been linked to chromosomes
13 and 17
Other genes are implicated
Colorectal Cancer

1 in 20 Americans will develop colorectal
cancer


Second only to lung cancer
Risk factors


Genetics
High-fat and low-fiber diet are contributors
Diabetes


Leading cause of blindness, heart disease, and
kidney failure
Two major types


Type 1 (insulin-dependent diabetes mellitus)
Type 2 (non–insulin-dependent diabetes mellitus)
Type 1 Diabetes




Autoimmune destruction of insulin-producing beta
cells in the pancreas
 T cell activation and autoantibody production
Onset before 40 years of age
Higher incidence with the offspring of diabetic
fathers
Recurrence risk


0.55 MZ twin concordance rate
1% to 6% sibling recurrence
Type 2 Diabetes




80% to 90% of all diabetes cases
Neither HLA nor autoantibodies are commonly seen
in type 2
Patient has insulin resistance or diminished insulin
production
Risk factors


High carbohydrate diet and obesity
Recurrence risk


0.90 MZ twin concordance rate
10% to 15% sibling recurrence
Obesity

Body mass index >30



Obesity is a substantial risk factor for heart disease,
stroke, and type 2 diabetes
Adoptive studies


BMI = W/H2 (weight in Kg and height in meters)
Body weights of adopted individuals correlated
significantly with their natural parents’ body weights
Twin studies

Higher concordance in MZ twins than DZ twins
Alzheimer Disease




Progressive dementia and loss of memory
Formation of amyloid plaques and neurofibrillary
tangles in the brain
Risk of developing AD doubles in individuals who
have an affected first-degree relative
Mutations in any of three genes that affect amyloidbeta deposition



Presenilin 1 (PS1)
Presenilin 2 (PS2)
Amyloid-beta precursor protein gene (APP)
Alcoholism


Alcoholism risk is 3 to 5 times higher in individuals
with an alcoholic parent
Adoption studies


Offspring of nonalcoholic parents, when reared by
alcoholic parents, did not have an increased risk
Twin studies

Concordance rates


MZ: >60%
DZ: <30%
Psychiatric Disorders

Schizophrenia




Severe emotional disorder characterized by delusions,
hallucinations, and bizarre, withdrawn, or inappropriate
behavior
Recurrence risk among the offspring of one affected
parent is 10 times higher than the general population
Twin and adoption studies indicate that genetic factors are
likely to be involved
Bipolar affective disorder


Genetics
Minimal environmental influence