Thoughtful Phenotype Definitions Empower Participants and Power Studies

Substantial advances in understanding the genetic architecture of complex traits have been achieved through large global collaborations that maximize sample size1 and strive for highly homogeneous phenotype definitions. Consequently, we have identified >500 genome-wide significant loci associated with 15 psychiatric disorders1. However, these associations have not yet yielded translational insights into disease; we have not identified new drugs or therapeutics based on these findings. Further, progress has been uneven, with the majority of associations in very large and homogeneous samples of primarily European origin2,3. In order to move towards our ultimate goal of precision psychiatry and consequently better outcomes for our patients, new strategies will be needed. Continuing to amass additional samples following the same approach as to date is unlikely to yield insights into psychiatric disorders with heterogeneous presentations (such as for example PTSD), to achieve functional insights, or to increase equity among our studies.

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