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Odds Ratio vs Relative Risk. Genetic studies of multifactorial diseases. Department of Medical Genetics Medical University of Warsaw. Probability – definition. Probability of an event P(A) denotes the frequency of it’s occurrence in a long (infinite) series of repeats.
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Odds Ratio vs Relative Risk Genetic studies of multifactorial diseases Department of Medical Genetics Medical University of Warsaw
Probability – definition • Probability of an eventP(A) denotes the frequency of it’s occurrence in a long (infinite) series of repeats Probability0.25 (1/4) indicates that certain event is observed in 1 from 4 or 25% occurrences It’s represented by a number in the range from 0 (event never occurs) to 1 (event occurs every time)
Odds • Odds - describe probability as a ratio (proportion) Odds take higher values than probability For example, if probability of getting ill is 1/5, the odds of getting ill is:
Odds vs. probability • Frequency of blue balls: 4/10 = 2/5 (two out of five balls are blue) • Proportion of blue balls vs. yellow balls: 4:6 = 2:3 (2 to 3)
Influence of the environment Polygenic diseases (multifactorial diseases) • Many genes involved • Multiple factors (including environmental ones) + genetically predetermined susceptibility to the action of these factors AD AR Polygenic
atherosclerosis hypertension diabetes neoplasms neurodegenerative diseases immunological disorders (rheumatoid arthritis, multiple sclerosis etc.) … and many others Polygenic diseases(examples)
Ethiology: single gene vs polygenic (multifactorial) New methods of analysis needed!
Genetic background of a disease – ideal study • Genotyping: everybody is genotyped and classified • Monitoring: occurrence of the disease is monitored for a long time • Comparison: frequency of the disease in two groups
Genetic background of a disease – ideal study (an example) 26% (n=128) Genotype (+) 15% (n=75) Genotype (-)
Comparing the risks - measures • Risk: % of affected individuals • Risk difference • Risk ratio (relative risk, RR) • Example - a disease occurred: - in 26% of individuals with given genotype- in 15% of the persons without the genotype Risk difference:26% - 15% = 11% Risk ratio (RR):26% /15% = 1.7
Comparing the risks- RD vs RR • If a disease is rare,the risk difference may be small,but the risk ratio – large ! • Example: - risk among those with genotype: R=1.5%- risk among those without: R =0.3% Difference= 1.5% - 0.3% = 1.2% Ratio(RR)= 1.5% /0.3% = 5.0
Comparing the risks- RD vs RR – which is better? • Difference – an absolute measure - Useful in estimating how many people are ill because of the genotype • Ratio – a relative measure - better for estimating the risk in a given patient - better for the purpose of basic studies
Affected Healthy (a+b) a b Genotype(+) observation Affected Healthy c d (c+d) Genotype(-) Comparing the risks- associations in a table = a/(a+b) / c/(c+d) RR = Proportion of frequency of affected among those withthe genotypeto the frequency of affected among those without the genotype
RR – relative risk Affected Yes No a b a Yes a + b RR = Genotype c d c c + d No
Affected Healthy (a+b) a b Genotype(+) observation Affected Healthy c d (c+d) Genotype(-) Comparing the odds – odds ratio (a table) = [a/(a+b) / (1-a/(a+b))] / [c/(c+d) / (1-c/(c+d))] OR Proportion of the odds among those withthe genotypeto the odds among those without the genotype
OR - odds ratio Affected a Yes No a + b a b a Yes 1 − a + b OR = Genotype c d c c + d No c 1 − c + d
OR calculated for occurrence of disease among those with vs. without the genotype
OR calculated for occurrence of genotype among those with vs. without the disease (cn.)
Comparing the risks- OR vs RR – rare diseases • If a disease is rare(both among those with and without genotype), RR and OR areverysimilar ! • Example: • Frequency of RA among • - those withHLA-DR4 - 0.018, • - the rest -0.003 • RR = 0.018/0.003 = 6.0 • OR = 0.01833/0.00301 = 6.09 • „rare” means<10%
Comparing the risks- OR vs RR – frequent diseases • If a disease is frequent, RR and OR aredifferent ! • Example: • - Risk in the presence of genotype =0.6 • - Risk in the absence of genotype = 0.1 : • RR = 0.6/0.1 = 6.0 • OR = 0.6/0.4 / 0.1/0.9 = 13.5 • „frequent” means>10%
7 493 496 4 OR vs RR – (practical considerations) Disease Genotype (+) Genotype Genotype (-) RR=(7/500)/(4/500) RR=7/4 the key factor: proportion 7/4 (considerable errorispossible)
Disease + - 493 700 7 493 Genotype - + 496 400 496 4 RR=1,76 OR=1,75 RR=1,31 OR=1,75 The error can be minimized by enlarging the group of affected RR has changed but OR has not ! Disease + Disease + - 493 707 + Genotype + = 404 496
RR is the preferred measure of strength of association between genotype and disease, esp. in a medical/diagnostic setting In practice it is easier to determine OR OR is a good approximation of RR,when the disease is rare (<10%) both in those with and without the genotype Conclusions
What to remember? When to use and how to calculate RR? Whendiseasesarefrequent >10% When to use and how to calculate OR? Whendiseasesarerare <10%