Genes, Environment-Lifestyle, and Common Diseases

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Genes, Environment-Lifestyle, and Common DiseasesChapter 5

Mosby items and derived items © 2006 by Mosby, Inc.

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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

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


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Multifactorial Inheritance Threshold model

Liability distribution Threshold of liability


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Multifactorial Inheritance


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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, 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


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Nature and Nurture Nature

Genetics Nurture

Environmental-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 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


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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)


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Familial Hypercholesterolemia


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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


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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


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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 the 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 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


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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


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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 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

Genes, Environment-Lifestyle, and Common Diseases

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