Genetic EpidemiologyLecture 13

PS Timiras

A Few Definitions• GENOME: THE COMPLETE SET OF GENES OF AN

ORGANISM

• GENOTYPE: THE GENETIC CONSTITUTION OF A CELL OR AN ORGANISM

• PHENOTYPE: THE OBSERVABLE PROPERTIES OF AN ORGANISM THAT HAVE DEVELOPED UNDER THE COMBINED INFLUENCES OF

ｷｷ The genetic constitution of the organism, and ｷｷ The effects of environment6al factors

• PHENOME: GENOME + ENVIRONMENT THE CONSTITUTION OF AN ORGANSIM COMBINING GENETIC AND ENVIRONMENTAL FACTORS

• Many of the changes in normal function and common diseases are known to have a genetic component

• Several thousands (7,000?) rare diseases are inherited in a Mandelian fashion

one gene one disease

• Many genes for the phenotype have been mapped better understanding of these changes

Correlation between Aging and Genetic Epidemiology

Correlation between Aging and Genetic Epidemiology

• Genetic variation interacts with the environment

to modify the risk of disease e.g. cancer

coronary heart diseaseneurologic, psychiatric diseases,

etc.

• Monogentic (one gene only) or multigenetic (several genes) may or the risk of developing a certain trait

Genetic Factors in Alzheimer’s DiseaseRisk of late onset AD or ¯depending on mutation type

The risk is (12 times) in the presence of AP0E4 (16 % of the general population carry this mutation)

The risk is ¯ halved in the presence of APO E2 ( 7% of the general population carry this mutation)

As in other complex genetic traitsthere is

an “incomplete correlation”between the APOE4 genotype and the APOE4 phenotype

APOE4 may contribute to AD risk, but may not, by its presence alone, cause the disease

In examining the role of genes in the

etiology of complex disease

we must distinguish:

1. causal genes: single gene mutation

leads to diseasee.g.Huntington disease

2.susceptibility genes: associated

with the disease butthemselves not

sufficient to cause the disease

1. Determination of familial aggregation

2. Determination of evidence of familial aggregation discrimination between environmental/cultural and genetic factors that may contribute

to the mutation clustering

3. Determination of genetic factors and their identification

Determination of genetic participation to disease

Complex disease genes express traits:

(a) that show no clear Mendelian inheritance (one gene/ one phenotype);

(b) but have moderate to high evidence of genetic inheritance;

(c) exhibit familial aggregation cases

(d) are either polygenic, that is, involve multiple genes or

(e) are multifactorial, that is, involve multiple genes interacting with the environment.

Ways in which genetic susceptibility may influence a disease:

(a) by itself,

(b) by making the carrier more susceptible to the disease, or

(c) by exacerbating the expression of a risk factor or the risk factor may exacerbate the genetic effects

Social /economic /ethical considerations “pro”

• For the elderly: “medical assistance denied or rationed“ arguments “pro”

• cost of medical care

cost of Medicare programsnot all elderly are

poor and those who are not

want to profit from Federal programs

Social /economic /ethical considerations

“Contra”

1.heterogeneity of elderly population

2.denying access to high technology care

1. to the elderly will not substantially

decrease overall health costs because most expenses are incurred in young

ages

3.difficulty in managing ethical choices and legal consequences

Cataract: example of complex genetic/environmental disease

Cause: hardening yellowing of the crystalline lens of the eye necessary for accommodation

Genetic factors: more frequent in females than malesprogresses with advancing ageis found in twinsmore frequent in light colored eyes

Environmental factors: diabetes exposure to ultraviolet light exposure to pollutants (e.g. tabacco smoke)

At Death Bed

Heroic Measures

Humanistic Medical Care

Pharmacogenetics or Pharmacogenomics

Individualization of drug treatment according to each

patient’s genetic constitution

(i.e.based on an understanding of the genetic basis in

patient responses to drugs)

A New Image of AgingFocuses

not only on treating diseases but also on preventing them by:

– improving physiologic competence

– better and continuing life-long education

– adopting healthier /hygienic lifestyles – promoting the discovery of new medical technologies