Beginning of the chapterSimple disease risk statistics

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GENETICS

Disease risk statistics

GENETICSHow do we know the risk?

Concept: Odds RatioThe risk of developing a disease due to a genetic variation

Example:

G = Functional gene (wild type)A = Mutated gene (mutant)

Diabetes gene

GENETICS

Everyone has two genes of each type (with a few exceptions)

A genetic variation may therefore occur on both, or only on one gene

Example:

The possible outcomes are:

G on both genes >> G/G >> Wild typeG on one, A on the other gene >> G/A >> HeterozygousA on both genes >> A/A >> Homozygous mutant

G = Functional gene (wild type)A = Mutated gene (mutant)

How do we know the risk?

G G

GA

A A

GENETICSHow do we know the risk?

G G GA A A

G/G A/G A/A

Wild type Heterozygous Homozygous mutant

The 3 possibilities:

OR:1 OR:2 OR:4

Normal risk of developing the

disease

DOUBLE risk of developing the

disease

QUADRUPLE risk of developing

the disease

GENETICSHow do we know the risk?

OR = 1.651.65-times risk of developing the disease65% higher risk

GENETICSHow do we know the risk?

GENETICSHow does the OR influence the

probability of developing a disease?

Example DEMO SYNDROME (very rare):1 risk gene variant exists (just an example) General population has “normal” risk (population average: OR = 1) 1 out of 100 000 suffers from the disease, 0.001% lifetime risk

ODDS RATIO relative to the POPULATION AVERAGE (ORpop):Population average: ORpop = 1Example OR for a woman: ORpop = 60

PROBABILITY OF DEVELOPING THE DISEASEAverage = 0.001% lifetime risk= 0.001% probability of developing the disease for ORpop = 1

What is the PROBABILITY OF DEVELOPING THE DISEASE for ORpop = 60?

= 0.06% probability of developing the disease

GENETICSHow does the OR influence the

probability of developing a disease?

Although with genetic variations the risk is 60 times higher, the probability of developing the

disease is only 0.06%

This genetic analysis is not relevant for health!

GENETICS

Examples of genetic influence on diseases

The disease occurs in approx. 5% of the population, genetic variations increase the risk to OR = 7>> probability of developing the disease increases from 5% to 30%RELEVANT!

The disease occurs in approx. 1%, genetic variations increase the risk to OR = 1.1>> probability of developing the disease from 1% to 1.1%NOT RELEVANT!

The disease occurs in approx. 1%, genetic variations increase the risk to OR = 60>> probability of developing the disease from 1% to 45% RELEVANT!

The disease occurs in approx. 0.001%, genetic variations increase the risk to OR = 90>> probability of developing the disease from 0.001% to 0.06% NOT RELEVANT!

The disease occurs in approx. 0.001%, mutations lead to developing the disease in all cases>> probability of developing the disease from 0.001% to 100% RELEVANT!

GENETICS

Why is the OR used for genetic analyses, instead of the probability of developing the disease?

OR 3

ALZHEIMER'S RISK

PREVENTION PROGRAMUNHEALTHY LIFESTYLE

OR 0.36 OR 0.6OR 1.4

3 x 0.36 x 0.6 = 0.64 OR Disease probability

13.46%

3 x 1.4 = 4.2 ORDisease probability60.82%

Disease probabilityaverage: 20%

GENETICS

Summary:

The genetic risk is stable and unchangeable. Different analyses of the same genes should yield the same OR, even when conducted

by different laboratories.

The disease probability is affected by Positive (OR smaller than 1) and Negative (OR bigger than 1) environmental influences.

Thus, the probability of disease cannot be reliably measured in the laboratory.

Why is the OR used for genetic analyses, instead of the probability of developing the disease?

GENETICS

The aim of preventive genetic analysis:

To predict the probability of developing a disease!

To positively influence the risk of developing the disease!

Why is the OR used for genetic analyses, instead of the probability of developing the disease?

End of the chapterSimple disease risk statistics

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