Transcript Genetic Epidemiology Lecture 13

Genetic Epidemiology
Lecture 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
The effects of environment6al factors
• PHENOME: GENOME + ENVIRONMENT
THE CONSTITUTION OF AN ORGANSIM
COMBINING GENETIC AND ENVIRONMENTAL
FACTORS
Correlation between Aging and Genetic Epidemiology
• 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
• Genetic variation interacts with the environment
to modify the risk of disease e.g. cancer
coronary heart disease
neurologic, 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 Disease
Risk 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 traits
there 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
disease
e.g.Huntington disease
2.susceptibility genes:
associated with the
disease but
themselves not sufficient
to cause the disease
Determination of genetic participation to 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
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
programs
not 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 males
progresses with advancing age
is found in twins
more 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 Aging
Focuses
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