Genes, Environment-Lifestyle, and Common Diseases

1. Genes, Environment-Lifestyle, and Common Diseases Chapter 5

2. 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

3. 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

4. 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

5. Multifactorial Inheritance • Threshold model • Liability distribution • Threshold of liability

6. Multifactorial Inheritance

7. Recurrence Risks • Recurrence risks of multifactorial diseases can change substantially because gene frequencies as well as environment and lifestyle factors can differ among populations

8. 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

9. Nature and Nurture • Nature • Genetics • Nurture • Environmental-lifestyle

10. 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

11. 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

12. Genetics of Common Diseases • Congenital malformations • Congenital diseases are present at birth or shortly after birth • Most congenital diseases are multifactorial

13. 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

14. 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)

15. Familial Hypercholesterolemia

16. 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

17. 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

18. 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

19. 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)

20. 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

21. 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

22. 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

23. 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)

24. 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%

25. 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