Risks for Relatives

Abstract

Studying risks for relatives of persons with a disease (affected probands) compared with relatives of persons without the disease (unaffected probands) can reveal important information on the likely causes of that disease. Even modestly increased risk for relatives cannot exist without there being strong underlying familial risk factors. Studying risks for relatives, including twins, as a function of the strength of genetic, environmental and cohabitational relationships to the probands can help resolve whether the familial risk factors are likely to have a genetic or environmental aetiology, the more so if specific genes and environmental exposures are measured for one or more of the family members. Because only a small proportion of the familial aggregations of common diseases can be explained by known genes and other familial causes, there is scope for greatly expanding our knowledge of disease aetiology through information that can be gained from studying risks for relatives.

Key Concepts

  • Discovering the familial causes of risks for relatives can reveal important information on the likely causes of diseases.
  • Even modestly increased risks for relatives cannot exist without there being strong familial factors.
  • Shared familial risk factors may be genetic or due to environment or cohabitation (such as infection, diet and shared social factors).
  • The effects on disease risk of genetic and nongenetic familial risk factors are often confounded (i.e. strongly correlated) but can potentially be separated by considering degree of relatedness and duration of living together (cohabitation) and living apart.
  • There is scope for greatly expanding knowledge about disease aetiology through studying risks for relatives.

Keywords: diseases; familial aggregation; genes; probands; shared environmental factors

Figure 1. Cumulative risk (%) and 95% confidence interval (95% CI) of breast cancer in the sisters, mothers and aunts of the case probands diagnosed with breast cancer before the age of 40, 40–49 and 50–59 years. Cumulative risk, bold line; 95% CI limits, thin line and cumulative risk in the population, dotted line. Note that, in each category of relatives, the risks decrease as the age at onset of the case proband increases. Reproduced from Dite et al.2003 © Oxford University Press.
Figure 2. Cumulative risk (%) and 95% confidence interval (95% CI) of breast cancer in the sisters, mothers and aunts of the case probands who were diagnosed with breast cancer before the age of 40 years and not identified to a carrier of a BRCA1 or BRCA2 mutation. These risks are shown for all relatives of that group, for those with another affected first‐degree relative (other than the case proband) and for those without an affected first‐degree relative (other than the case proband). Cumulative risk, bold line; 95% CI limits, thin line and cumulative risk in the population, dotted line. Reproduced from Dite et al.2003 © Oxford University Press.
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Further Reading

Elston RC, Olson JM and Palmer L (2002) Biostatistical Genetics and Genetic Epidemiology. Chichester, UK: Wiley.

Thomas DC (2004) Statistical Methods in Genetic Epidemiology, chap. 5. New York, NY: Oxford University Press.

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Hopper, John L, Dite, Gillian S, and Byrnes, Graham B(Jan 2017) Risks for Relatives. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005423.pub2]