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. 2018 Jan 15;18(1):135.
doi: 10.1186/s12889-018-5033-5.

The surprising implications of familial association in disease risk

Morten Valberg  1   2 , Mats Julius Stensrud  3 , Odd O Aalen  3
Affiliations

The surprising implications of familial association in disease risk

Morten Valberg et al. BMC Public Health. .

Abstract

Background: A wide range of diseases show some degree of clustering in families; family history is therefore an important aspect for clinicians when making risk predictions. Familial aggregation is often quantified in terms of a familial relative risk (FRR), and although at first glance this measure may seem simple and intuitive as an average risk prediction, its implications are not straightforward.

Methods: We use two statistical models for the distribution of disease risk in a population: a dichotomous risk model that gives an intuitive understanding of the implication of a given FRR, and a continuous risk model that facilitates a more detailed computation of the inequalities in disease risk. Published estimates of FRRs are used to produce Lorenz curves and Gini indices that quantifies the inequalities in risk for a range of diseases.

Results: We demonstrate that even a moderate familial association in disease risk implies a very large difference in risk between individuals in the population. We give examples of diseases for which this is likely to be true, and we further demonstrate the relationship between the point estimates of FRRs and the distribution of risk in the population.

Conclusions: The variation in risk for several severe diseases may be larger than the variation in income in many countries. The implications of familial risk estimates should be recognized by epidemiologists and clinicians.

Keywords: Familial association; Familial relative risk; Gini index; Inequality; Lorenz curve.

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Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
a The familial relative risk (FRR) as a function of the individual relative risk (IRR) defined in terms of the dichotomous model in Expression (1) and (2), assuming one or two diseased family members, respectively. b The IRR as a function of the FRR. 1% of the population belong to the high-risk group (q=0.1) in both panels
Fig. 2
Fig. 2
a, c) The familial relative risk (FRR) as a function of the individual relative risk (IRR) defined in terms of the dichotomous model in Expression (1) and (2), assuming one or two diseased family members, respectively. b, d) The IRR as a function of the FRR. 50% (q=0.5) and 80% (q=0.8) of the population belong to the high-risk group in panels a, b) and c, d), respectively
Fig. 3
Fig. 3
The familial relative risk (FRR) as a function of the proportion, q, of the population belonging to the high-risk group defined in terms of the dichotomous model in Expression (1) and (2), assuming one or two diseased family members, respectively. The individual relative risk (IRR) is 20
Fig. 4
Fig. 4
The Lorenz curve (a) and 400 samples (b) from a beta distribution resulting from a familial relative risk of 2.3 and E[P]=0.01, representing Parkinson’s disease
Fig. 5
Fig. 5
The distribution (a) of a beta distributed variable P, and its corresponding Lorenz curve (b), for three selected familial relative risks (FRRs). The expected value of P is set to 0.01. The 10% at highest risk (shaded area) account for 26%, 33%, and 65% of the diagnoses in the three scenarios, respectively
See this image and copyright information in PMC

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