Predictive value of testing for multiple genetic variants in multifactorial diseases: implications for the discourse on ethical, legal and social issues

Abstract

Multifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a
complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk
of disease. Unraveling the genetic origins of these diseases is expected to lead to individualized medicine, in
which the prevention and treatment strategies are personalized on the basis of the results of predictive genetic
tests. This great optimism is counterbalanced by concerns about the ethical, legal, and social implications of
genomic medicine, such as the protection of privacy and autonomy, stigmatization, discrimination, and the
psychological burden of genetic testing. These concerns are translated from genetic testing in monogenic
disorders, but this translation may not be appropriate. Multiple genetic testing (genomic profiling) has
essential differences from genetic testing in monogenic disorders. The differences lie in the lower predictive
value of the test results, the pleiotropic effects of susceptibility genes, and the low inheritance of genomic
profiles. For these reasons, genomic profiling may be more similar to nongenetic tests than to predictive tests
for monogenic diseases. Therefore, ethical, legal, and social issues that apply to predictive genetic testing for
monogenic diseases may not be relevant for the prediction of multifactorial disorders in genomic medicine.