In order to increase the genetic homogeneity of the sample, and thus increase the power of the study, we attempted to select patients as rigorously as possible. Patients of German descent were recruited within a joint research project and were stratified for male gender and an early age at onset, a combination of traits which is associated with increased heritability.32,33 Prior studies have shown that population stratification in Germansare small.40,86,87 Thus, at the time when SNPs for the follow-up study were chosen, we had not applied a formal test to control for population stratification. A post-hoc principal components analysis (PCA)88(EigenSoftv1.01; http://www.genepath.med.harvard.edu/∼reich/Software.htm) and genomic control analysis42 (showing a lambda of 1.099) had no major impact on the significance level of our 15 SNPs (see Supplementary Online Content, eTable 4), thus confirming these prior obervations.
