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Genes, Environment-Lifestyle, and Common DiseasesChapter 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
Variation in traits caused by the effects of multiple genes
Multifactorial trait 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
BMI = W/H2 (weight in Kg and height in meters) Obesity is a substantial risk factor for heart disease,
stroke, and type 2 diabetes Adoptive studies
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 amyloid-
beta 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
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