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Understanding variation in disease risk: the elusive concept of frailty.

Aalen OO, Valberg M, Grotmol T, Tretli S - Int J Epidemiol (2014)

Bottom Line: Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance.We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals.Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates.

View Article: PubMed Central - PubMed

Affiliation: Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway o.o.aalen@medisin.uio.no.

No MeSH data available.


The familial relative risk, r, associated with a diseased sibling as a function of s according to formula (1) in the text, where s denotes the relative risk associated with a change in a risk factor from mean minus two standard deviations to mean plus two standard deviations. The familial correlation, , is set to 0.5. Based on normally distributed variation in risk.
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dyu192-F3: The familial relative risk, r, associated with a diseased sibling as a function of s according to formula (1) in the text, where s denotes the relative risk associated with a change in a risk factor from mean minus two standard deviations to mean plus two standard deviations. The familial correlation, , is set to 0.5. Based on normally distributed variation in risk.

Mentions: In order to get a deeper understanding, one has to consider statistical models. The familial risk association depends on two conditions, namely the correlation between the risk factors within a family, and the variation in risk within the population associated with these factors. Assume that the risk depends exponentially on normally distributed risk factors with a correlation ρ, and that s denotes the relative risk associated with a change in the risk factor from mean –2 standard deviations (SD) to mean + 2SD. The familial relative risk, r, associated with a diseased sibling is given by:(1)r=exp{ρ(lns)2/16},which is a special case of a more general formula given by Aalen.65 Assume for instance that ρ = 0.5 which is a very strong familial correlation. Then formula (1) as a function of s is plotted in Figure 3. One sees that even for s = 10, which represents a very strong effect of the risk factor, the value of r is still less than 1.2. Hence, for simple polygenetic inheritance at the risk factor level, the familial relative risk associated with even strong risk factors is very moderate.Figure 3.


Understanding variation in disease risk: the elusive concept of frailty.

Aalen OO, Valberg M, Grotmol T, Tretli S - Int J Epidemiol (2014)

The familial relative risk, r, associated with a diseased sibling as a function of s according to formula (1) in the text, where s denotes the relative risk associated with a change in a risk factor from mean minus two standard deviations to mean plus two standard deviations. The familial correlation, , is set to 0.5. Based on normally distributed variation in risk.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588855&req=5

dyu192-F3: The familial relative risk, r, associated with a diseased sibling as a function of s according to formula (1) in the text, where s denotes the relative risk associated with a change in a risk factor from mean minus two standard deviations to mean plus two standard deviations. The familial correlation, , is set to 0.5. Based on normally distributed variation in risk.
Mentions: In order to get a deeper understanding, one has to consider statistical models. The familial risk association depends on two conditions, namely the correlation between the risk factors within a family, and the variation in risk within the population associated with these factors. Assume that the risk depends exponentially on normally distributed risk factors with a correlation ρ, and that s denotes the relative risk associated with a change in the risk factor from mean –2 standard deviations (SD) to mean + 2SD. The familial relative risk, r, associated with a diseased sibling is given by:(1)r=exp{ρ(lns)2/16},which is a special case of a more general formula given by Aalen.65 Assume for instance that ρ = 0.5 which is a very strong familial correlation. Then formula (1) as a function of s is plotted in Figure 3. One sees that even for s = 10, which represents a very strong effect of the risk factor, the value of r is still less than 1.2. Hence, for simple polygenetic inheritance at the risk factor level, the familial relative risk associated with even strong risk factors is very moderate.Figure 3.

Bottom Line: Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance.We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals.Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates.

View Article: PubMed Central - PubMed

Affiliation: Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway o.o.aalen@medisin.uio.no.

No MeSH data available.