APPROACHES TO THE GENETICS OF CARDIOVASCULAR-DISEASE THROUGH GENETIC FIELD WORK

Successful molecular genetic studies of complex disease require tract, careful phenotypization, which is more difficult than that performed for monogenic diseases. We have developed a family-oriented field work ing approach, which relies on index patients, their primary care physi cians, and a minimum number of field working staff. The patients are r esponsible for recruiting their family members. Packets containing an explanatory pamphlet, an informed consent statement, a questionnaire, and blood cuvettes are provided. Data are transferred from questionnai re and from the laboratory into a computer program that facilitates co nstruction of the family tree. We have applied this genetic field work ing approach primarily to patients with lipid disorders. Coupling resu lts from genetic field working with modern DNA diagnostic tests such a s the oligonucleotide ligation assay, has enabled us to effectively id entify patients with familial hypercholesterolemia in the German popul ation. We are now extending genetic field working to hypertension. Hyp ertension is much more difficult to study, because the phenotype is mo re difficult to discern and document. Both complex diseases have the d isadvantage that the parents of the index patients are likely to alrea dy be dead. Nevertheless, we concentrate on the recruitment of large p edigrees, sibling pairs with parents whenever possible, and trios cons isting of index patient and both parents or index patient, parent and sibling. With these constellations we can conduct association studies, linkage analysis, and novel combinations of both approaches.