What a rheumatologist should know about genetics

Abstract

Rheumatic diseases are generally non-mendelian, depending on an interaction between genetic susceptibility and environmental factors. The overall role of genetic factors can be estimated from family resemblances and twin studies, while the role of individual susceptibility genes is studied by lod score analysis, haplotype sharing and population associations. Linkage analysis allows a long-range search of chromosomes for susceptibility loci, while population associations depend on much shorter-range effects. It is often very hard to tell whether an association of a disease with a marker is because the marker confers susceptibility or because it is in linkage disequilibrium with a separate susceptibility gene. When searching for individual susceptibility genes, it is important to avoid postulating models which would require an unrealistically high degree of genetic determination of the disease.