Mitchell BL, Thorp JG, Wu Y, et al. - Researchers sought to determine how different definitions of depression used in genetic studies are associated with estimation of major depressive disorder (MDD) and phenotypes of MDD.

• A case-control polygenic risk score analysis was performed including patients with a diagnosis of MDD drawn from the Australian Genetics of Depression Study and controls and patients with self-reported depression drawn from QSkin.

• There were a total of 12,106 individuals with major depressive disorder.

• Sample size of the discovery genome-wide association studies was identified to be the major factor in estimating risk.

• Studies assessing diagnostic criteria for major depressive disorder yielded polygenic risk scores that had correlations with higher odds ratios with somatic symptoms and comorbidities of major depressive disorder.

• Priority should be given to larger genome-wide association study sample sizes to develop potential better genetic estimations of risk for severe depression, regardless of the depth of phenotyping.