A strength of this study is that we applied phenotypic strategies aimed at detecting genetic variants that play a central but non-specific role in AD susceptibility. This is counter to the approach taken in most psychiatric genetic studies which generally apply case-control comparisons for specific clinical diagnoses, sometimes followed by adjunct cross-disorder analyses. However, it has long been recognized that clinical nosology poorly reflects etiological mechanisms, with both genetic and environmental risk factors showing non-specific effects across disorders. ADs, despite their heterogeneous clinical presentations, likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems (12). Given the value of fear and anxiety for survival, there are likely sets of evolutionarily-conserved genes that regulate these basic biological responses. This is supported by twin studies that identify factors of common genetic risk across ADs in addition to disorder-specific genetic factors. With this in mind, we applied and compared two strategies for combining information across clinical phenotypes. The first is a simple CC approach, comparing cases defined as having “any AD” against supernormal controls. The second applied
