This study had significant strengths including a five-nation cooperative and coordinated case and control ascertainment consortium, comprehensive phenotyping that was carefully designed and coordinated, and gene selection procedures designed to optimize findings. Nonetheless, the study was underpowered, limiting our ability to detect significant effects. After FDR corrections, the smallest P-value observed was 0.2125 for SNP rs4791362 on gene GLP2R for the All AN analyses. This corresponds to a relative risk of 1.3, 1.2, and 1.2 for minor allele frequencies of 0.10, 0.25, and 0.40. Using statistical power of 0.80, in a 1:1 unmatched case/control study, the minimum sample sizes needed to obtain significance for these relative risks are approximately 4,050, 4,270, and 3,430, respectively, three to four times the number of the participants in this study. Lack of power is a common problem faced by consortia studying the genetics of relatively rare phenotypes such as AN. Statistical power was particularly weakened as case numbers dropped with the increasingly restrictive definitions of AN. Our approach to case definition was based on previous findings (i.e., stronger linkage signals with more restrictive case
