Mapping Genes for Common Diseases: Statistical Planning, Power, Efficiency and Informatics

After a decade or so of progress with the identification of major genes, the emphasis has shifted towards genes for common diseases (complex traits). Real successes have been few so far. There has been a gradual appreciation of the difficulties presented by genes that have a relatively small individual phenotypic effect and which may show complex interactions. Furthermore, there may be different genetic determinants of the disease in different populations together with environmental effects and practical difficulties in obtaining sufficiently large samples of suitable material for analysis. At the same time, analytical methods have been in flux with many new tests and variations on existing methods appearing in the literature. The choice of analytical strategy is determined to a large extent by the nature of the disease and the DNA resources that can be obtained. Some assessment of power to detect a genetic locus can be useful; however, this may be of limited value given the ignorance of the nature of the genetic basis of the disease. Consideration of the efficiency of different approaches is also important and careful statistical planning should be undertaken.