Description This ICRP Publication reviews data on naturally occuring multifactorial diseases and develops a mathematical model to predict the impact
of radiation-induced mutations on the frequencies of these diseases in the population. It provides a broad outline of the aetiological
features and examples of multifactorial diseases. It considers the concepts and models used to explain their inheritance patterns, with
particular emphasis on the Multifactorial Threshold Model. Conceptual differences from 'mendelian' diseases are discussed, and pertinent
epidemiology is reviewed. Particular attention is paid to diabetes mellitus and to coronary heart disease. Mechanistic models in population
genetics are considered. The concepts of liability, threshold, mutation-selection balance, and mutation component are integrated into
a Finite Locus Threshold Model as a basis for risk estimation. The relevance of these findings for estimation of radiation risk of multifactorial
diseases is discussed.
2.1
General aspects. 2.2 Congenital abnormalities. 2.3 Isolated congenital abnormalities. 2.4 Impact of advances in medicine on the incidence
of congenital abnormalities. 2.5 Summary
3. Models of Inheritance of Multifactorial Diseases.
3.1 The Standard multifactorial
threshold model (MTM). 3.2 Other models. 3.3 Summary.
4. General Attributes and Epidemiological Aspects of Chronic Multifactorial
Diseases.
4.1 Conceptual differences between mendelian and multifactorial disease. 4.2 Overall prevalences and epidemiolgical
features of chronic multifactorial diseases. 4.3 Summary.
5. Diabetes Mellitus.
5.1 Epidemiological and clinical aspects.
5.2 Type 1 diabetes mellitus (IDDM). 5.3 Type 2 diabetes mellitus (NIDDM). 5.4 Summary.
6. Essential Hypertension.
6.1
Epidemiology. 6.2 Risk factors. 6.3 Family and twin studies. 6.4 Candidate genes and polymorphisms. 6.5 Hypertension and the risk of
stroke and coronary heart disease (CHD). 6.6 Hypertension and the risk of congestive heart failure and end-stage renal disease. 6.7 Summary.
7. Coronary Heart Disease.
7.1 Epidemiology. 7.2 Risk factors. 7.3 Family and twin studies. 7.4 Variability in total cholesterol
levels in the population and its relationship to coronary heart disease. 7.5 Genetic risk factors other than hyperlipidaemia. 7.6 Summary.
8. Mechanistic Models on the Maintenance of Multifactorial Traits in the Population.
8.1 The models of Crow and Kimura. 8.2
The models of Lande and Turelli. 8.3 Other models. 8.4 Conclusions. 8.5 Summary.
9. General Conclusions from Studies of Multifactorial
Diseases and their Relevance for Risk Estimation.
10. The Concept of Mutation Component of Genetic Diseases and its Application for
estimating the Responsiveness of Mendelian Diseases to an Increase in Mutation Rate.
10.1 Background. 10.2 The mutation component
concept. 10.3 Mutation component for autosomal dominant diseases. 10.4 Effect of the presence of sporadics on mutation component of autosomal
recessive diseases. 10.5 Mutation component for X-linked recessive and autosomal recessive diseases. 10.6 Summary.
11. A Finite-Locus
Threshold Model for Estimating the Mutation Component of Multifactorial Diseases.
11.1 The finite-locus threshold model. 11.2
Computer simulations: general procedure and results on the relationship between heritability and mutation component. 11.3 Strengths and
potential limitations of the model and other considerations. 11.4 Conclusions. 11.5 Summary.
12. Relevance for Radiological Protection.
12.1 Introduction. 12.2 Background on the use of the doubling dose method for risk estimation. 12.3 The 1993 UNSCEAR estimates of genetic
risk. 12.4 The risk estimates of ICRP (Publication 60) for multifactorial diseases. 12.5 The conclusions of the Task Group in the context
of those of Publication 60. 12.6 Are revisions of genetic risk estimates by the Commission warranted now? 12.7 Summary.
Annals of the ICRP Volume 29/3-4
