Chapter 5
Genes, Environment, and Common
Diseases
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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
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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
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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
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Multifactorial Inheritance

Threshold model


Liability distribution
Threshold of liability
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Multifactorial Inheritance
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Multifactorial Inheritance

Characteristics of multifactorial disorders

Result from hereditary and environmental
factors
 Hereditary component is polygenic
• Individual involved genes follow mendelian principles
• Many genes act together to influence the expressed
trait
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Multifactorial Inheritance

Concordance and discordance

Concordance
• Expression of the disease in two related family
members

Discordance
• Expression of the disease in one family member but
not a second
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Multifactorial Inheritance

Twin studies and concordance

Genetic conditions
• Monozygotic (MZ) twins: 100% concordance
• Dizygotic (DZ) twins: less than 100% and similar to
that among other siblings


Environmental conditions
• Equal concordance rates among MZ and DZ twins
Multifactorial conditions
• MZ twins with greater concordance than DZ twins, but
rates are not 100%

Adoption studies

Gene-environment-lifestyle interaction
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Recurrence Risks

Recurrence risks of multifactorial diseases
can change substantially because gene
frequencies as well as environment and
lifestyle factors can differ among populations
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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, recurrence risk is
higher
Recurrence risk is higher if the proband is of
the less commonly affected sex
Recurrence risk for the disease usually
decreases rapidly in remotely related
relatives
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Nature and Nurture

Nature


Genetics
Nurture

Environment-lifestyle
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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
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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
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Genetics of Common Diseases

Congenital malformations


Congenital diseases are present at birth or shortly
after birth
Most congenital diseases are multifactorial
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Adult Multifactorial Diseases

Coronary heart disease

Potential mycocardial infarction 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
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Familial Hypercholesterolemia




Autosomal dominant
1 in 500 is heterozygous for 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)
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Familial Hypercholesterolemia
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Hypertension



Risk factor for heart disease, stroke, and
kidney disease
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
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Breast Cancer





Affects 12% of American women who live to
85
If a woman has a first-degree relative with
breast cancer, her risk doubles
Recurrence risk increases if age of onset in
the affected relative is early and if the cancer
is bilateral
An autosomal dominant form (5%) has been
linked to chromosomes 13 and 17
Other genes are implicated
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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
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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)
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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 offspring of diabetic
fathers
Recurrence risk


0.55 MZ twin concordance rate
1% to 6% sibling recurrence
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Type 2 Diabetes




80% to 90% of all diabetes cases
Neither HLA nor autoantibodies commonly
seen in type 2
Person 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
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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
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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
amyloid-beta deposition



Presenilin 1 (PS1)
Presenilin 2 (PS2)
Amyloid-beta precursor protein gene (APP)
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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%
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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
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