Investigating complex traits in diverse populations, especially when samples are pooled from different research sites or cultural contexts, requires consistency and equivalence in the underlying construct and assessment measures across groups. Differences and variability in phenotypic measurement between study sites and populations may affect both gene discovery and the transferability of genetic findings between populations. Most psychiatric classification systems and diagnostic measures have been developed and validated in individuals from industrialized, Western societies (Henrich et al., 2010). This presents a substantial challenge for global and cross-cultural collaborations. Investigations into cross-cultural differences in the prevalence of major depression, for instance, have suggested that although there is a shared underlying disorder construct across groups (Kendler et al., 2015; Simon et al., 2002), individuals may differ culturally in terms of the level of symptomatology reached prior to seeking help (Simon et al., 2002). The inclusion and consideration of diverse populations in the development, validation, and deployment of diagnostic measures used in genetic studies is therefore critical for ensuring an unbiased picture of disease etiology (Supplemental Methods VII).
