Aims: Progress has been made in identifying mutations that confer susceptibility to complex diseases, with the prospect that these genetic risks might be used in determining individual disease risk. In this paper we use Crohn’s disease (CD) as a model of a common complex disorder, and develop methods to estimate disease risks using both genetic and environmental risk factors.
Method: Calculations use three independent risk factors: CARD15 genotype (conferring a gene dosage effect on risk), smoking (2-fold increased risk for smokers), and residual familial risk (estimating the effect of unidentified genes, after accounting for the contribution of CARD15). Risks are estimated for high-risk individuals who are siblings, parents and offspring of a CD case.
Results: The CD risk to the sibling of a CD case who smokes and carries two CARD15 mutations is approximately 35%, which represents a substantial increase on the population risk of 0.1%. In contrast, the risk to a non-smoking sibling of a CD case who carries no CARD15 mutations is 2%. Risks to parents and offspring were lower.
Conclusions: High absolute risks of CD disease can be obtained by incorporating information on smoking, family history and CARD15 mutations. Behaviour modification through smoking cessation may reduce CD risk in these individuals.
- Crohn's disease
- risk estimation