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

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

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

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

Mosby items and derived items © 2006 by Mosby, Inc. 5 Multifactorial Inheritance  Threshold model Liability distribution Threshold of liability

Mosby items and derived items © 2006 by Mosby, Inc. 6 Multifactorial Inheritance

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

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

Mosby items and derived items © 2006 by Mosby, Inc. 9 Nature and Nurture  Nature Genetics  Nurture Environmental-lifestyle

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

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

Mosby items and derived items © 2006 by Mosby, Inc. 12 Genetics of Common Diseases  Congenital malformations Congenital diseases are present at birth or shortly after birth Most congenital diseases are multifactorial

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

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

Mosby items and derived items © 2006 by Mosby, Inc. 15 Familial Hypercholesterolemia

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

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

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

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

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

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

Mosby items and derived items © 2006 by Mosby, Inc. 22 Obesity  Body mass index >30 BMI = W/H 2 (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

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

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

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