Another issue of potential concern is population stratification. It is generally assumed that association between a genetic variant and the phenotype of interest arises due to linkage disequilibrium (close location of two genes on the chromosome resulting in their co-inheritance), however, association can also result from spurious sources. Most commonly, spurious association is caused by population stratification, when the studied population is composed of subgroups that differ with respect to both the genetic marker allele frequency and the studied phenotype (see Hamer and Sirota (2000) for a nice didactic example). A number of ways to deal with this issue have been proposed, the most simple of which is to ensure maximum homogeneity of the studied sample with respect to racial and ethnic ancestry. Detailed discussion of these and other methodological issues is outside the scope of this review; interested reader can consult more specialized literature on this subject (Tiwari et al., 2008).
