Chapter 5 - genes, environment-lifestyle, and common diseases

incidence rate

• number of new cases of a disease reported during a specific period divided by the number of individuals in the population

• Ex. How many cases of covid in 2020

prevalence rate

• the proportion of the population affected by a disease at a specific point in time

• Varies population to population

relative risk

• chance of developing a disease relative to an exposure

• Factors - age, gender, diet, exercise and family he of the disease

polygenic traits

• effects of multiple genes causes dystrophin the variations in traits

• Focus is on the genes - usually many (poly) genes

Multifactorial traits

• environmental factors cause the variations in traits

Quantitative traits

• are measured on a continuous numeric scale

• Follow a normal bell curve for distribution

Liability distribution

• does not follow the bell-shaped distribution

• Appears to be either present or absent in individuals

• Does not follow the inheritance patterns expected of single-gene diseases

• Has low end of getting disease compared with a high end of getting disease

Threshold of liability

below the threshold an individual appears normal, above the threshold the disease affects the person

Threshold model example

• pyloric stenosis

• Neural tube defects

• Cleft lip

• Club foot

• Some forms of congenital heart disease

Empirical risks

• based on direct observation of data

• Specific for each multi factorial disease

multifactorial diseases - recurrence risk

• hard to determine

• Substantially change because the genes causes dystrophin frequencies, environment, and lifestyle factors can different among population

• Higher if more than one family member is affected

• Proband is of the less commonly affected sex then the recurrence risk is higher

• Disease expression in the proband is more severe risk is more severe

Nature

• is the genetic makeup of an individual, which influences their development, traits, and susceptibility to diseases, often interacting with environmental factors.

Nurture

• refers to the environmental influences, experiences, and lifestyle choices that shape an individual's development and health outcomes, interacting with their genetic predispositions.

Which research strategies are used to estimate the relative influence of genes and environment

• twin studies - usually compare between MZ & DZ twins

• Adoption studies

Monozygotic (MZ) twins

• identical twins

• Natural clones

Dizygotic (DZ) twins

• fraternal

Concordant trait

• both members of a twin pair share a trait

Discordant trait

• twin pair does not share a trait

Adoption studies

• child born to parents who have a disease but are then subsequently adopted by parents lacking the diseases are studied for disease recurrence

Gene-environment interaction

• a genetic predisposition may interact with an environmental factors cause to increase the risk for disease to a much higher level then either factor would alone

Congenital malformations

• congenital disease are present at birth

• Most are multifactorial

• Environmental factors can cause congenital malformations

• Occur during fetal development

Coronary heart disease

• potential myocardial infarction caused by atherosclerosis in the arteries supplying blood to the heart

• Coronary heart disease is a condition characterized by the narrowing or blockage of coronary arteries due to atherosclerosis, which can lead to a myocardial infarction or heart attack.

• Possible cerebrovascular accident (stroke) caused by atherosclerosis in the arteries supplying blood to the brain

Risk increase for coronary heart disease

• more affected relatives exist

• Affected relatives are female rather than male

• Age of onset is younger than 55 years

Autosomal dominant - coronary heart disease

• hyperchloseterolemia

• High-fat diet

• Lack of excerise

• Smoking

• Obesity

• ALL increase risk

Hypertension - multifactorial disorder

• characterized by high blood pressure arising from a combination of genetic, environmental, and lifestyle factors that impact heart health.

• Environmental factors - sodium intake, stress, obesity lack of exercise

• 20 - 40 % BP variations are genetic, rest environmental

• BP regulation is complex

Cancer - multifactorial disorder

• second leading cause of death in US

• resulting from a combination of genetic predispositions, lifestyle choices, and environmental exposures.

• Tobacco use accounts for 1/3rd of all cancers

Breast cancer - multifactorial disorder

• affects 12% of American women who live to 85 years of age

• Woman has a 1st degree relative with breast cancer, then her risk is double

• Recurrence risk increases if the age of onset in the affected relatives is early and if the cancer is bilateral

• Autosomal dominat form (5% to 10%) has been linked to chromosomes 13 (BRCA2) and 17 (BRCA1)

  • This form causes 50 to 80% lifetime risk of developing breast cancer and increases the risk for ovarian cancer

  • Males with this gene at increase risk for prostate cancer

Colorectal cancer

• second to lung cancer in the number of deaths occurring annually in the US

• Risk 2 to 3x higher with affected 1st degree relative

• Inherited adenomatous polyps is coli (APC) gene mutations play a vital role in familial adenomatous polyps is

• Somatic mutations are involved in common colon cancers

• Mutations in any 6 genes cause hereditary nonpolyposis colorectal cancer

• Environmental factors - high fat, low fiber diet

Prostate cancer

• loss of heterozygosity in some regions

• Detected by digital examination and prostate specific antigen (PSA) test

• 2scd most diagnose in men second to skin cancer

• 2scd most cause of death in men second to lung cancer

• Risk factor - high fat diet

Diabetes mellitus - multifactorial disorder

• complex not fully understood

• Leading cause of blindness, heart disease and kidney failure

• 2 major types

  • Type 1

  • Type 2

type 1 diabetes

• insulin dependent diabetes mellitus

• Caused by autoimmune destruction fo insulin producing beta cells in the pancreas

• Need insulin for life

• Siblings of individuals with type 1 face a substantial elevation in risk

• Diabetic father - incidence higher in offspring

Type 1 diabetes - twin studies

• MZ and DZ pairs have 30 to 50% and a 5 to 10% increased risk

• Association of specific human leukocyte antigen (HLA) class ll alleles is 40%

Insulin gene

• genetic variation here is associated with a 10% increased risk

Type 2 diabetes - multifactorial disorder

• 90% of individuals with diabetes have type 2

• Neither HMC associations nor autoantibodies are present

• Insulin resistance is preset or insulin production is diminished

• Risk factors - obesity and a positive family history

• Excessive has preventive effect

Recurrence risk - type 2 diabetes

• MZ twins have a 90% risk

• First-degree relatives have a 15% to 40% risk

Genes - type 2 diabetes

• variant of TCF7L2 associated with a 50% increased risk

• PPAR-y and KCNJ11 associated with increased risk

Glucokinase gene

• associated with maturity - onset diabetes of the young

how is type 2 diabetes treated

• with lifestyle modification including diet and exercise

Obesity - multifactorial disorder

• BMI greater than 30

• Presents a substantial risk factor for heart disease, stroke, cancer, and type 2 diabetes

Gene - obesity

• leptin and its receptors are related to obesity

adoption studies - obesity

• body weights of adopted individuals correlated significantly with their natural parents body weights

Twin studies - obesity

• genetics have an effect on body weight - most studies yielded heritability estimates between .60 and .80

Alzheimer’s disease (AD) - multifactorial disorder

• results in progressive dementia and a loss of memory

• Produces amyloid plaques and neurofibrillary tangles

• Risk doubles if a 1st degree relative has AD

Mutations early on set - Alzheimer’s disease

• affect amyloid-beta deposition

  • Prensenilin 1 (PS1)

  • Presenilin 2 (PS2)

  • Amyloid-beta precursor protein (APP) gene

  • All the primary cause of AD

mutations for late onset - Alzheimer’s disease

• Allelic variation (e2, e3, e4) in apolipoprotein E (APOE)

• One copy of the e4 allele - 2 -5x greater risk

• 2 copies of the e4 allele - 5-10 x more likely develop AD

Alcoholism - multifactorial disease

• risk is 3 to 5 times higher in indivuals with an alcoholic parents

Adoption studies - alcoholism

• offspring of an alcoholic parent, even when raised by nonalcoholic parents have a fourfold increased risk

• Offspring of nonalcoholic parents, when reared by alcoholic parents, did not have an increased risk

Twin studies - alcoholism

• MZ and DZ pairs have a >60% and <30% respectively increased risk

Genes - alcoholism

• individuals with ALDH2×2 allele are much less likely to become alcoholics

• Allelic variations of gamma-aminobutyric acid (GABA) receptors increase the risk

Schizophrenia - multifactorial disorder

• recurrence risk among offspring of one affected parent is 10 times higher than the general population

• If one has affected sibling and parent they are at 20% increase risk

• 2 affected parents 50% increase risk

Twin & adoption studies yielded heritability- schizophrenia

• MZ and DZ pairs have a risk of 47% and 12% respectively

• If schizophrenia parents but adopted at same risk due to biology

Genes - schizophrenia

• brain expressed genes whose products interact with glutamate receptors have been implicated

Schizophrenia and bipolar disorder

• both are heterogeneneous

• Reflect the influence of numerous genetic and environmental factors, making the phenotype hard to identify and genetic analysis complicated

Bipolar affective disorder - multifactorial disorder

• is also called manic depressive disorder

• Risk rises between 5-10% if individual has affected 1st degree relative

• characterized by mood swings that include emotional highs (mania or hypomania) and lows (depression).

Twin & family studies - bipolar affective disorder

• show 60% or bipolar risk is due to genetic factors

• 30% of the risk for unipolar disorder is due to genetics

Unipolar disorder

• major depression

Genes - bipolar affective disorder

• serotonin

• Dopamine

• Noradrenaline