This study benefits from precision in diagnostic assessment of AD, known alcohol exposure in a majority of the controls, and careful quality control that excluded overlap of individuals between studies. Despite these strengths, our sample size was insufficient to identify additional GWS loci robustly. Power analyses indicate that additional SNPs associated with AD are likely to have small effect sizes, smaller than schizophrenia47 and more consistent with more common psychiatric disorders (e.g. major depression48). This supports the pressing need for collection of large numbers of well characterized cases and controls. The differences between our results and the study of AUDIT scores18 highlight that ascertainment and trait definition are critically important and must be taken into account. Careful study of how screening tools, such as the AUDIT, correlate to genetic liability to AD (as defined by DSM-IV or similar) could substantially boost sample sizes for future AD GWAS. There is also a continued need to characterize the genetic architecture of AD in non-EU populations.
