POWER CONSIDERATIONS IN THE GENETICS OF DIABETES AND OTHER COMMON CHRONIC CONDITIONS

Critical to the success of studies to identify genes involved in commo n chronic diseases such as NIDDM is sufficient statistical power to de tect linkage of markers with putative disease loci. It is clear that f or diseases such as NIDDM, the sampling design most widely used is bas ed on affected sibling pairs. Analyses of such data then use a variety of model-free approaches that rely on the expected increased allele s haring for affected pairs at loci involved in the disease. Power is a function of the number of sibling pairs available. It is also a functi on of the density of the genetic map used, the number of hypothesized disease loci, whether the data are restricted to sibling pairs where a t least one parent is unaffected, the manner in which allele frequenci es at the marker locus are estimated, and the statistical procedure ch osen. These issues are illustrated in the context of NIDDM. The princi ples apply to other common diseases as well. It is anticipated that th e joining of genotyping technology, appropriate statistical techniques , and adequate pedigree data will lead to the identification of specif ic genes for the common diseases and result in understanding that will lead to preventing or slowing the onset and development of these dise ases.